In this study we observed the effects in vivo of hyperthermic treatment on the cell kinetics (cell proliferation/cell death) in one case of human non-Hodgkin lymphoma, by analyzing the following morpho-cytochemical parameters: Acridine Orange fluorochromasia, mitotic index, proliferating cell nuclear antigen (PCNA) expression, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) labeling, and ultrastructure morphology. After two hyperthermic exposures there was a significant reduction of cell growth rate (e.g. mitotic and PCNA positive cells) and an increase in cell loss by death. The cell death occurred by the typical apoptotic cascade, namely DNA fragmentation, chromatin hypercondensation and margination, karyorrhexis, ribonucleoproteins segregation and cytoplasm cleavage; in addition some necrotic cells were found. The data indicates that the hyperthermic treatments limit the cell proliferation (e.g. arrest and/or deceleration of the cell cycle) by facilitating the trigger of programmed cell death. It was concluded that thermal injury can be considered an effective inducer of antiproliferative and apoptogenic associated effects on the growth of this kind of neoplasia.

In human therapy, an absence of cross-resistance has been observed between vincristine and vindesine in patients receiving polychemotherapy whilst, in our experimental in vivo studies, such a cross-resistance has been found between Vinca alkaloids. Further studies are required to explain this discrepancy.

L-Arginine (Arg) is classified as an essential amino acid for birds, carnivores and young mammals and a conditionally essential amino acid for adults. It is converted by arginase to L-ornithine, a precursor of polyamines and urea, which is important in the urea cycle. Arg serves as a precursor for, creatine, which plays an essential role in the energy metabolism of muscle, nerve and testis and accounts for Arg catabolism and for the synthesis of agmatine and proteins. Via its ability to increase growth hormone secretion it influences immune function. Depending on nutritional status and developmental stage, normal plasma Arg concentrations in humans and animals range from 95 to 250 mumol/l. Systemic or oral Arg administration has been shown to improve cardiovascular function and reduce myocardial ischemia in coronary artery disease patients, It reduces blood pressure and renal vascular resistance in essential hypertensive patients with normal or insufficient renal function. Although Arg plasma concentrations are not altered in hypercholesterolemic individuals, oral or intravenous Arg administration can reverse endothelial dysfunction in hypercholesterolemic patients and in cigarette smokers. The main importance of Arg is attributed to its role as a precursor for the synthesis of nitric oxide (NO), a free radical molecule that is synthesized in all mammalian cells from L-Arg by NO synthase (NOS). NO appears to be a major form of the endothelium-derived relaxing factor (EDRF). NO and EDRF share similar chemical and pharmacological properties and are derived from the oxidation of a terminal guanidine group of L-Arg. Various mechanisms have been implicated in the defect in vascular relaxation. These include, increased diffusional barrier for NO, L-Arg depletion, altered levels of reactive oxygen, inactivation of NO by superoxide anions (O-2(-)). The independent reactions of O-2(-), NO and their reaction yielding peroxynitrite are critical in the initiation and maintenance of the atherosclerotic state and contribute to the defect in vasorelaxation: NO also plays a role as a neurotransmitter, mediator of immune response and as signaling molecule. The NO synthesized by iNOS in macrophages contributes to their cytotoxic activity against tumor cells, bacteria and protozoa. Our aim here is to review on some amino acids with high functional priority such as Arg and to define their effective activity in human health and pathologies. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

AIM: To present the 4 to 9 years (median: 6 years) treatment follow up of 10 HIV1-AIDS patients, 9 at AIDS and 1 at A(3) stages. METHODS : We have applied from 1992 to 1994, AZT combined with 2 integrase inhibitors, acriflavine and hydroxy-methyl-ellipticine. We could shift, in 1994, to combinations of 3 drugs including two more retrotranscriptase inhibitors (RTI), ddI and ddC, and, after 1995, to combinations of 4 drugs including also two other RTI, d4T and 3TC, and 3 protease inhibitors (PI), indinavir, ritonavir, and saquinavir. In 1998, as cobalamine was shown by an in vitro test, to act as integrase inhibitor, vitamin B12 was added in cycles of various lengths. Every three weeks, not only the investigations were repeated, but the virostatics were changed. RESULTS : No grade 2 virostatics toxicity has been registered. The viral loads (VL) decreased according to exponential curves. Their initial parts obeyed first order kinetics, The second parts were and still are asymptotic. The first parts could be rectilinear or sinuous. The sinuosities were associated to cofactors present before treatment (chimerism, UV irradiation, hepatitis C or B and C, brain toxoplasmosis). The asymptotic parts, whose VL were below PCR detectable levels, presented discrete, reversible HIV1 rebounds, associated to other cofactors ( such as herpes zoster, herpes 6, CMV, flat condyloma, and influenza). Among immunologic parameters, the monocyte and CTL numbers increased and presented, during the rapidly decreasing part of VL curve, a significant inverse correlation with it. Neither CD4(+) nor suppressor T-cell (STC) numbers presented such correlation. Near 100 % of CTL were CD28(+). Later, vitamin B12 applications increased monocyte and CD28(+) CTL numbers, and appeared to reinforce VL stabilization. CONCLUSION: The combinations of inhibitors affecting 3 retrovirus targets, retrotranscriptase, integrase, and protease have given to 10 out of 10 AIDS patients survivals varying today between 4 to 9 years, in excellent conditions. The UVA-pretreated patient is the only one presenting a not maximally reduced asymptotic VL, while his CD4(+) and STC have been absent for 8 years. Other patient VL regressed exponentially to become asymptotic, below PCR detectable levels.

L-Arginine (Arg) is classified as an essential amino acid for birds, carnivores and young mammals and a conditionally essential amino acid for adults. It is converted by arginase to L-ornithine, a precursor of polyamines and urea, which is important in the urea cycle. Arg serves as a precursor for creatine, which plays an essential role in the energy metabolism of muscle, nerve and testis and accounts for Arg catabolism and for the synthesis of agmatine and proteins. Via its ability to increase growth hormone secretion it influences immune function. Depending on nutritional status and developmental stage, normal plasma Arg concentrations in humans and animals range from 95 to 250 micromol/l. Systemic or oral Arg administration has been shown to improve cardiovascular function and reduce myocardial ischemia in coronary artery disease patients. It reduces blood pressure and renal vascular resistance in essential hypertensive patients with normal or insufficient renal function. Although Arg plasma concentrations are not altered in hypercholesterolemic individuals, oral or intravenous Arg administration can reverse endothelial dysfunction in hypercholesterolemic patients and in cigarette smokers. The main importance of Arg is attributed to its role as a precursor for the synthesis of nitric oxide (NO), a free radical molecule that is synthesized in all mammalian cells from L-Arg by NO synthase (NOS). NO appears to be a major form of the endothelium-derived relaxing factor (EDRF). NO and EDRF share similar chemical and pharmacological properties and are derived from the oxidation of a terminal guanidine group of L-Arg. Various mechanisms have been implicated in the defect in vascular relaxation. These include, increased diffusional barrier for NO, L-Arg depletion, altered levels of reactive oxygen, inactivation of NO by superoxide anions (O2-). The independent reactions of O2-, NO and their reaction yielding peroxynitrite are critical in the initiation and maintenance of the atherosclerotic state and contribute to the defect in vasorelaxation. NO also plays a role as a neurotransmitter, mediator of immune response and as signaling molecule. The NO synthesized by iNOS in macrophages contributes to their cytotoxic activity against tumor cells, bacteria and protozoa. Our aim here is to review on some amino acids with high functional priority such as Arg and to define their effective activity in human health and pathologies.

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies.

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 mumol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis: In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid,is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to a-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

We have analyzed by morphological (TEM) and histochemical (TUNEL reaction) criteria the type of cell death occurring in one case of human multiple myeloma after hyperthermia. Samples of cells examined immediately at the end of two treatments with a 15-day interval showed a significant degeneration, mostly demonstrating features of apoptosis (cell shrinkage, DNA fragmentation, karyorrhexis). The possible causes of the lag period between heating and apoptosis onset-expression are discussed.

Two virostatics which we discovered in 1990, acriflavine (ACF) and hydroxy-methyl-ellipticine (HEL) and shown active on HIV1 resistant to AZT have been introduced into combinations of four virostatics selected among ten available: themselves, plus zidovudine, zalcitabine, didanosine, lamivudine, stavudine, saquinavir, ritonavir, indinavir, the combinations were applied in 3-week sequences, differing from each other by drug rotation. Those which contained ACF may have more often a CD34 decrease than those containing neither ACF nor HEL, and they present more often a CD4 increase. No significant difference as far as side effects or beneficial effects could be detected after 18 months to 6 years, between sequences containing ACF or HEL or both, and sequences not containing any one of them.

This paper presents the evolution during its follow-up of a virostatic combination study of the type I-II trial conducted on ten AIDS-related complex (ARC) or acquired immunodeficiency syndrome (AIDS) patients [1, 9, respectively]. Its concept is based on the following original notions: a) it is not the number of the virostatics applied to each patient at any phase which determines their effect: it is the number of affected virus targets which determines the effect. Thus, the so called "tritherapies", imposed by the "AIDS Command" to thousands of patients selected at random, to be compared to the same number of subjects receiving only "bi" or "monotherapies", might be beginning to face failure because they attack only two targets: retro-transcriptase and HIV, protease. Having discovered, owing to our experimental screening, original HIV, virostatics, acriflavine (ACF) and several ellipticine analogues among which we have used methyl-hydroxy-ellipticine (MHE), we are able to attack two virus targets unaffected by classical virostatics: ACF attacks DNA, from its integrated double branched stage to the provirus one, and MHE inhibits topoisomerase II. We experimentally combined these two agents with AZT, which inhibits retro-transcriptase, thus we realized a combination affecting three targets. This three agent combination was able to eradicate Friend's virus from infected mice. Clinically, combinations of three drugs affecting four targets (as they are selected among the ten virostatics available today) give a stronger result than three drug combinations affecting only three targets, because they were selected from the five virostatics which were the only ones available at the beginning of the present study. Five patients out of five who received the combinations of four virostatics chosen among the ten currently available (thus affecting four targets) from the beginning of their treatment to the present have all reduced their viral load (VL) and maintained it below the delectable level (< 200 RNA copies/mL then 20 copies/mL); b) as the toxicities of virostatics and as HIV, resistances may happen as soon as 12 weeks of treatment, the combinations have been, in our study, applied in shorter (3 week) sequences, differing from each other due to drug rotation; c) neither toxicity nor resistance occurred; d) curiously, the CD4 numbers, even when they increased rapidly, has never attained their normal count, and their curve may be a Gombertzian one. This CD4 restoration limitation can be due to persisting virus, as indicated in some patients by small peaks which may appear on some VL plateaus, though they disappear without treatment change.Our thesis proposes the possibility that this CD4 restoration handicap may be due to a possible latent GVH due to a micro-allo-chimerism, which we could demonstrate in two of seven carefully studied patients.

The author has focused the subject on the perduration of puberty thymus involution as a cause of immunity aging, a term in which he does not include senescence. The decrease between immune reactions against HIV1 at 25 years of age and those at 35 is considerable; the decrease is also indirectly revealed by spontaneous tumor exponentially growing incidence after 40 years in man and its equivalent, 16 months in mice: the immunity parameters indicate a regression correlated with this incidence growth. He regrets the neglect of suppressor cell and anti-idiotype problems by the basic immunologic research. Given the role of cofactors non specifically related to the antigen, such as that CD28 and its ligands, he suggests the interest to approach immunology via the science of chaos and fractals, which would be more appropriate than classical methodology to study highly complex phenomena on which apparently minimal interventions may induce considerable effects.

Using ultrastructural analysis, we studied the effects of hyperthermic treatment of one case of human liver metastasis from colon carcinoma. The results indicate that the main hyperthermic response involves the neoplastic and the histiocytic cell population. The drastic decrease in metastatic cells was accompanied by the appearance of cell fragments and apoptotic bodies. Consequently, the histiocytic component (Kupffer cells) showed increased frequency, indicating an activated state. The data are consistent with a direct action of the heat on tumor cells with subsequent activation of Kupffer cells.

After a review of the recent physiologic, cellular genetic and molecular genetic acquisitions, a critical comment of the proposed classification is presented concerning especially a) the inclusion in the so-called ”precursor B-lymphoblastic leukemias”, which are pre-B neoplasias, of Burkitt's leukemic lymphoma, the cells of which are sIg+, hence B and not pre B; b) the inclusion in the chronic B lymphocytic leukemia of the so-called Galton's “prolymphocytic” leukemia, the cells of which are also sIg+, thus B and not pro B. In fact, the transformed blastoid medium size cells of this leukemia present the markers of the plasmablasts, which are the precursors of the long-lived plasma cells and migrate from the lymphoid tissue T-zone to bone marrow, where they secrete IgD, or G, or E, or to the mucosae, where they secrete IgA. Thus the so called “B-prolymphocytic leukemia” is the leukemic conversion of the (blastoid medium size cell) plasmablast lymphoma. There is in the new classification, a “large cell lymphoma” entity, which makes redundance with the “large cell follicle centre lymphoma”. This large cell lymphoma representes a heterogen complex, as it includes the B-immunoblastic lymphoma which is not presented as an entity. As far as T lymphomas are concerned, it is not indicated that the CD8 cells may be CD57 + or −, and CD28 + or −. It could be mentionned that the cytotoxic T-cells are CD8+ C57− CD28+, while the suppressor T-cells are CD8+ CD57+ CD28.

We reported in the first part of this editorial [1] and in an article on AIDS therapy with five HIV1 virostatics applied in two then three, or initially three, or initially four agent combinations, given in 3 week sequences differing from each other due to drug rotation [2], the contrast between: a) the decrease of viral load, possibly below the detectable level, b) the absence of effect on the helper CD4(+), the CD8(+) C57(-) cytotoxics and the CD8(+) C57(+) suppressor cells. We proposed a thesis according to which the HIV1-AIDS complex might have another pathogenic component other than HIV1, ie, a microchimerism graft-versus-host reaction (GvH) or an autologous GvH-like reaction [1].Shifting from five to 10 virostatics owing to the availability of lamivudine or 3TC [3], stavudine or d4T [4] and three HIV1 protease inhibitors, saquinavir [5], ritonavir [6] and indinavir [7], applied according to the same modality, we have enhanced the reduction of viral load, and significantly decreased the CD8(+) C57(+) suppressor cell counts, and increased those of the CD8(+) C57(-) cytotoxic cells.This result which indirectly shows the role of HIV1 in the increase of suppressor CD8(+) cells, hence in the late loss of immune memory and of opportunistic infections [8], reinforces :he thesis of a role, in AIDS pathogenesis, of a latent GvH reaction activated by HIV1 primo-infection, and its evolution from the hyperplastic phase to the hypoplastic one, which, inducing severe immune suppression, is responsible for HIV1 active infection relapse after the so-called latent phase [1]. Hence the proposition we make, of an indication of CD4 modulation with non specific immunotherapy by bestatin [9], of which we showed the effect in another population of HIV1-AIDS complex patients [10]. Its effect can be potentiated by tuftsin [11, 12]. When the suppressor cell number goes up over that of the cytotoxic one after the HIV1 active infection relapse, interferon gamma could be added, which, by amplifying the CD28 pathway [13] on CD8(+) cytotoxics, while suppressor cells lack CD28 [14], which might reestablish a ratio of suppressor over cytotoxic cells nearer to normal.It remains that the role of the five secondarily included agents in the decrease of suppressor cells will only be attributed with certainty and entirely to their virostatic effect, if it is shown that none of them exerts a selective anti-suppressor cell action.

The purpose of the present study was to evaluate by morphological approaches (light and electron microscopy), the effect of hyperthermic treatment in one case of human liver metastasis. The results demonstrate that hyperthermia causes a significant reduction of the metastatic cells circulating into sinusoids and the “normalization” of the hepatocytes substructure. The data are consistent with a direct and/or indirect action of the temperature on the presence of infiltrating tumor cells. Particular importance is attributed to a general activation of lysosomes present in neoplastic cells, Kupffer cells and hepatocytes.

We reported in the first part of this editorial and in an article AIDS therapy with five HIV1 virostatics applied in two then three, or initially three, or initially four agent combinations, given in 3 week sequences differing from each other due to drug rotation, the contrast between: a) the decrease of viral load, possible below the detectable level, b) the absence of effect on the helper CD4+, the CD8+ C57- cytotoxics and the CD8+ C57+ suppressor cells. We proposed a thesis according to which the HIV1-AIDS complex might have another pathogenic component other than HIV1, ie, a microchimerism graft-versus host reaction (GvH) or an autologous GvH-like reaction. Shifting from five to 10 virostatics owing to the availability of lamivudine or 3TC, stavudine or d4T and three HIV1 protease inhibitors, saquinavir, ritonavir and indinavir, applied according to the same modality, we have enhanced the reduction of viral load, and significantly decreased the CD8+ C57+ suppressor cell counts, and increased those of the CD8+ C57- cytotoxic cells. This result which indirectly shows the role of HIV1 in the increase of suppressor CD8+ cells, hence in the late loss of immune memory and of opportunistic infections, reinforces the thesis of a role, in AIDS pathogenesis, of a latent GvH reaction activated by HIV1 primo-infection, and its evolution from the hyperplastic phase to the hypoplastic one, which, inducing severe immune suppression, is responsible for HIV1 active infection relapse after the so-called latent phase. Hence the proposition we make, of an indication of CD4 modulation with non specific immunotherapy by bestatin, of which we showed the effect in another population of HIV1-AIDS complex patients. Its effect can be potentiated by tuftsin. When the suppressor cell number goes up over that of the cytotoxic one after the HIV1 active infection relapse, interferon gamma could be added, which, by amplifying the CD28 pathway on CD8+ cytotoxics, while suppressor cells lack CD28, which might reestablish a ratio of suppressor over cytotoxic cells nearer to normal. It remains that the role of the five secondarily included agents in the decrease of suppressor cells will only be attributed with certainty and entirely to their virostatic effect, if it is shown that none of them exerts a selective anti-suppressor cell action.

Before the discovery of HIV1 and HIV2, I proposed as the mechanism of HIV1-AIDS complex, a graft versus host reaction (GvH) induced by transfusion or seringe or sexual act blood transferred lymphocytes: this was based on the clinical, pathological and biological, and especially immunological similarities. I have treated ten HIV1-AIDS complex patients in the last phase with five virostatics, distributed in three week sequence combinations of 3 or 4, each differing from the preceeding and following ones. After follow-up between one and three and a half years, the results can be summarized as such: when the viral loads fall below the detectable level, the CD8+ CD57+ suppressor T-cell and CD8+ CD57- cytotoxic T-cell numbers tend towards normal levels (approximately 200/mL), but the CD4 counts go up to a maximum of only 394, far from the normal level (800). Moreover, none of these subsets present a significant coefficient of correlation with the HIV1 load, which indicates that these immunologic markers and the viral one provide different information. I suggest the hypothesis according to which HIV1-AIDS complex comprises other components than HIV1 infection, such as a) the evoked GvH, which would occur early enough and might explain this CD4 incomplete restoration by virostatics, and b) cytomegalovirus (CMV) activation which occurs later. The second part of this editorial review will be published in a part II of the "Dossier" on AIDS. It will be devoted to the discussion of GvH and CMV infection systematic treatments.

An intra-lymphatic injection of methyl-hydroxy-ellipticine at the dose of 50 mg was able ro reduce, in an advanced AIDS patient, the viral load by half and the pelvic adenopathy, evaluated with lymphangiography, by a third.

Recently we described the ''macrophagic lysosomal exocytosis'' (MLE) as a possible new mode of cancer cell death induced by hyperthermia (HT) [1]. In order to confirm this first report, HT was applied at the peritoneum level with perfusional procedure, after catheter insertion under local anesthesia. We evaluated the subcellular changes of peritoneal macrophages in human gastric tumor, before and after hyperthermic treatment at 42 degrees C for 90 minutes. Transmission electron microscopy showed that treatment produced the disappearance of the cytoplasmic granules, with a consequent extracellular scavenger action of the phagocytic cells, the proliferation of some organelles such as mitochondria, endoplasmic reticulum and Golgi complex that may be addressed to a subsequent restoration of the granular pool in the degranulated macrophages. This phenomenon can enhance the already documented effect of hyperthermic perfusional chemotherapy in peritoneal tumors.

Adult thymectomized C57/Bl (H-2b) and DBA/1 (H-2q) female mice were subjected to treatment with rat anti-mouse CD8 and mouse anti-rat Ig (kappa) prior to entering their third pregnancy with CBA/Ca (H-2k) males. The treatment protocol drastically reduced the number of CD8 (Ly2)-carrying lymphocytes (T-cytotoxic/suppressor phenotype) in the spleen and para-aortic lymph nodes, as assessed by immuno-staining. All mice were investigated on day 18 of their third gestation. The following data were collected from experimental and control groups: (1) resorption frequency, (2) weight of the placenta, fetuses, spleen and para-aortic lymph nodes, (3) immunohistochemical analysis of maternal lymphoid tissues, (4) level of antipaternal IgG serum antibodies, (5) content of “background” IgM and IgG-secreting cells in spleen and para-aortic lymph nodes. Neither the resorption frequency nor placental/fetal weight was affected by anti-CD8 treatment. However, the formation of anti-paternal antibodies was enhanced in anti-CD8 treated C57/B1 mice.