Considerable efforts are still needed in the public health sector, as well as in clinical, social and basic research, to improve programmes for HIV-1 MTCT (mother-to-child transmission) prevention and care. Advantage should be taken of the remarkable amount of expertise and resources that have accumulated over the past few years to accelerate the process of integration. Future initiatives should include integrating specialists and people with diverse backgrounds and targeting their scientific and programmatic ideas to address real-world problems in the area of MTCT of HIV-1.

PROBLEM:The aim of the present study was to define the expression of CXCR4 and CCR5 on non-cultured non-stimulated primary human trophoblast cells (TCs) immediately after their immunopurification.METHOD OF STUDY:We have evaluated by flow cytometric analysis and immunofluorescence, highly purified primary TCs prepared from first trimester (8.2 +/- 0.3 weeks, n = 15) and term (Caesarean section, n = 10) placentae for the cell surface and intracellular expression of CXCR4 and CCR5.RESULTS:There was a high level of individual variability for CXCR4 and CCR5 expression between trophoblast batches. In first trimester and term placentae TCs, we found a greater number of TCs preparations expressing intracellular CXCR4 than CCR5 (P < 0.05). Both receptors were predominantly localized in the intracellular compartment of TCs, whatever if isolated from first trimester or term placentae.CONCLUSIONS:The functional consequences of the predominance of CXCR4 expression and of cellular addressing are briefly discussed.

In utero transmission of HIV-1 has been demonstrated and may account for around 10-20% of all materno-fetal HIV-1 transmission. The possible routes for such transmission are transannexial or transplacental. In both cases, the microenvironment (cytokines and chemokines) at the placental interface could be an important regulatory factor in viral transmission.We therefore performed explant cultures of placental villi, and isolated purified trophoblasts, from term placentae obtained from HIV-1-seropositive and HIV-1-seronegative women in order to assess and compare the cytokine and chemokine secretion profiles using ELISA and semiquantitative RT-PCR.No major differences could be seen in the secretions of cytokines and chemokines at the level of whole placental tissue in HIV-1-positive and HIV-1-negative women. However, variations were observed in the expression of inflammatory cytokines and chemokines from trophoblastic cells, depending on the status of HIV-1 infection of the mothers but not the babies, all of which remained uninfected. The significance of these data is discussed.

PROBLEM: Implantation of human embryo requires expression of inflammatory cytokines and local attraction of T cells and natural killer (NK) cells. Chemokines are chemoattractants for these cells in classical inflammation. We speculated that they could also be involved in implantation.METHOD OF STUDY: We assessed by enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry the presence of three classical beta chemokines Macrophage Inflammatory Protein 1 (MIP1)alpha, MIP1 beta and Regulated upon activation, normal T cells expressed and secreted (RANTES) in cultures of placental villi or isolated trophoblasts derived from human first trimester and term placenta.RESULTS: Explant culture assays were positive for these three chemokines, with important quantitative variations between individuals. Half of the highly purified trophoblasts cultures were found by ELISA and RT-PCR to secrete in vitro MIP1 alpha and MIP1 beta. RANTES was never detected by ELISA in trophoblasts cultures, albeit we could detect a low amount of messenger RNA. Immunohistochemistry experiments show that Hofbauer cells and the trophoblast layer are a secretion site of MIP1 beta in term placenta, and that cytotrophoblasts are able to secrete this chemokine in early placenta.CONCLUSION: Human placenta is a site of secretion of chemokines that could be involved in establishment of pregnancy.

Several genetic subtypes and circulating recombinant forms (CRFs) of HIV-1 have been identified. The greatest degree of genetic diversity is displayed by variants from Central and West Africa. HIV-1 env C2-V5 and protease sequences were obtained from 15 HIV-1-infected pregnant women, who were selected from a larger cohort study in Yaoundé, Cameroon. Fourteen of 15 virus variants were shown to be recombinant, whereas a single variant appeared to be nonrecombinant subtype A. Five viruses were subtype A/J recombinants, with env genes derived from subtype A and protease genes derived from subtype J. Seven viruses clustered with reference sequences for CRF02 AG(IbNG) in both the env and protease gene fragments, and were thus subtype A/G recombinants. Two variants displayed even more complex recombination patterns. Phylogenetic analyses indicated that the five subtype A/J recombinants might be the first representatives of a previously unrecognized CRF.

In this study, coreceptor usage of HIV-1 other than subtype B in relation to HIV-1 transmission from mother to child was investigated. Repeated sampling of 42 HIV-1-seropositive, asymptomatic women in Cameroon during the second and third trimesters of pregnancy, at delivery, and 6 months postpartum were performed. Env subtyping was carried out from uncultured peripheral blood mononuclear cells (PBMCs) by heteroduplex mobility assay and, whenever necessary, by DNA sequencing. Virus isolates were tested for coreceptor usage on human cell lines-U87.CD4 and GHOST(3)-engineered to express stably CD4 and the chemokine receptors CCR1, CCR2b, CCR3, CCR5, or CXCR4, or the orphan receptors BOB/gpr15 or Bonzo/STRL33/TYMSTR. Transmission rate was 11.9%. Viruses were predominantly envelope subtype A and used CCR5 as coreceptor and, surprisingly, 4 of 28 (14.2%) isolates from mothers and 1 of 3 isolates from children used the orphan receptor Bonzo as well. In 2 transmitting mothers from whom sequential HIV-1 isolates were available, viral coreceptor usage evolved from CCR5 monotropic to CCR5/Bonzo dual tropic during pregnancy, and in 1 case transmission of this virus could be documented. Our data suggest that evolution of HIV-1 coreceptor usage to dual (or multi-) tropism may occur during pregnancy.

We examined CD4 and major HIV-1 co-receptor expression by trophoblast cells (TC) from early placentas, and the permissiveness of TC for infection by several natural HIV-1 isolates in vitro. Ten early placentas (4-6 weeks of gestation) from HIV- women were obtained after elective abortion. CD4 and HIV-1 co-receptor expression by TC was examined in terms of both mRNA and protein. The same TC were then challenged with three clinical HIV isolates of known phenotype, two originating from mothers who transmitted the virus to their child and one from a vertically infected newborn. TC infection was detected by polymerase chain reaction. CD4 expression was detected in five of the 10 placentas, while membrane protein expression of CCR3, CXCR4 and CCR5 was detected in every case, despite quantitative differences among individuals. Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations. TC from seven out of eight placentas were permissive to HIV entry, but no productive viral replication was detected (reverse transcriptase activity in culture supernatants). Interestingly, the addition of chemokine(s) or a CD4-blocking antibody to the cultures failed to inhibit TC virus entry. These data point to marked interindividual variability in HIV co-receptor expression by trophoblast cells and show that TC from early placentas can be infected in vitro by clinical HIV-1 isolates. They also suggest that viral entry in vitro might occur through a mechanism independent of both CD4 and chemokine receptors.

PROBLEM:To understand the mechanisms preventing and/or facilitating maternofetal transmission of human immunodeficiency virus (HIV)-1 across the placenta during pregnancy. METHODS OF STUDY:Current experimental data were reviewed. RESULTS AND CONCLUSIONS:The data about the production of cytokines by placental cells and explants, taken together with information indicating selective passage of certain HIV-1 variants across the placental trophoblast, suggest an intricate regulatory network operating at the fetomaternal interface. The data show a differential differentiation of early and late trophoblasts, as far as HIV entry routes are concerned. We believe this explains the relative predominance of the early infection window, as far as in utero infection is concerned. Whether such a differentiation state can be transiently induced on term placental trophoblasts by several differentiation agents, including cytokines, is being investigated. Whatever the results may be, it is obvious that infection of placental cells is an excellent model of passage infection by HIV of/through a mucosal barrier.

An atypical HIV-1 strain (CAM001) was identified in a pregnant Cameroonian woman in 1995. HMA subtyping of the env region was unsuccessful, and sequence analyses were performed. Unique sequence moths were found at the V3 tip (GAGRALHA and GAGRAWIHA), and phylogenetic studies showed that the env C2-V5 sequence branched within group M but remained distinct from all known HIV-1 subtypes, while p17 gag branched with the subtype F sequences. Four other HIV group M viruses, undetermined by BMA, of African origin were found to cluster with CAM001 in the C2-V5 sequences. With the BLAST method, we found in databases three strains whose V3 sequences also clustered with CAM001, These unusual env sequences from eight HIV-1 strains derived from Cameroon formed a separate cluster in HIV-1 group M, which we designated k.

PROBLEM: To understand the mechanisms preventing and/or facilitating maternofetal transmission of human immunodeficiency virus (HIV)‐1 across the placenta during pregnancy. METHODS OF STUDY: Current experimental data were reviewed. RESULTS AND CONCLUSIONS: The data about the production of cytokines by placental cells and expiants, taken together with information indicating selective passage of certain HIV‐1 variants across the placental trophoblast, suggest an intricate regulatory network operating at the fetomaternal interface. The data show a differential differentiation of early and late trophoblasts, as far as HIV entry routes are concerned. We believe this explains the relative predominance of the early infection window, as far as in utero infection is concerned. Whether such a differentiation state can be transiently induced on term placental trophoblasts by several differentiation agents, including cytokines, is being investigated. Whatever the results may be, it is obvious that infection of placental cells is an excellent model of passage infection by HIV of through a mucosal barrier.

We investigated HIV-1 diversity by means of heteroduplex mobility assay (HMA) genotyping. We studied 199 samples from patients originating from 26 countries and living in France. The HMA successfully genotyped 182 (91%) of these samples, as follows: 77 (42%) subtype A, 57 (31%) subtype B, 5 (3%) subtype C, 5 (3%) subtype D, 8 (4%) subtype E, 22 (12%) subtype F, 5 (3%) subtype G, and 3 (2%) subtype H. We were not able to genotype 12 samples by means of the HMA. These latter strains were sequenced, and phylogenetic analyses revealed that they were highly divergent subtype A-, D-, or G-related strains. Eight (of 12) subtype D strains were indeterminate by HMA, owing to the broad intrasubtype diversity, suggesting that new reference subtype D plasmids are required, as previously proposed. Thirty-seven strains belonging to the different subtypes were sequenced, and the results showed perfect concordance with the HMA results. Interlaboratory quality controls confirmed the reliability of the HMA for HIV-1 subtyping, despite the extensive viral variability. However, plasmid selection must be continuously revised to cover viral diversification.

PROBLEM: The paradigm of local suppression necessary to understand the survival of the fetal allograft is often compared with the host-tumor relationship.METHODS: We investigated two components of local immune suppression: placenta-induced immunosuppression, which is mediated at least in part by a soluble factor of low molecular weight that can induce anergy in lymphocytes, and interleukin-10 (IL-10).RESULTS: We show that enhancement of IL-10 production in the decidua and placenta after alloimmunization requires the presence of Asialo GM1+ cells. Placenta-induced immunosuppression is linked with defects in phosphorylation of some components of the T cell receptor.CONCLUSION: NK cells could be in fact regulatory cells pushing maternal immune response toward a Th2 profile, beneficial for fetal survival, or toward a Th1 type of immune response, which acts in synergy. Modulation of TcR may represent a new mechanism for maternal-fetal tolerance.

Infectious Diseases in Obstetrics and GynecologyVolume 5, Issue 2 p. 73-92 Research Article Immunopathology of early pregnancy Gérard Chaouat, Corresponding Author Gérard Chaouat INSERM, Hôpital Antoine Béclére, Clamart, FranceU 131 INSERM Hôpital Antoine Béclére, 92140 Clamart, FranceSearch for more papers by this authorElisabeth Menu, Elisabeth Menu INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorBarbara Mognetti, Barbara Mognetti INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorMarléne Moussa, Marléne Moussa INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorVéronique Cayol, Véronique Cayol INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorYakoute Mostefaoui, Yakoute Mostefaoui INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorSylvie Dubanchet, Sylvie Dubanchet INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorPhilippe Khadel, Philippe Khadel INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorJean Luc Voluménie, Jean Luc Voluménie INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorCatherine Bertrand Rongiéres, Catherine Bertrand Rongiéres INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorGeneviéve Lapprée Delage, Geneviéve Lapprée Delage INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this author Gérard Chaouat, Corresponding Author Gérard Chaouat INSERM, Hôpital Antoine Béclére, Clamart, FranceU 131 INSERM Hôpital Antoine Béclére, 92140 Clamart, FranceSearch for more papers by this authorElisabeth Menu, Elisabeth Menu INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorBarbara Mognetti, Barbara Mognetti INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorMarléne Moussa, Marléne Moussa INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorVéronique Cayol, Véronique Cayol INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorYakoute Mostefaoui, Yakoute Mostefaoui INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorSylvie Dubanchet, Sylvie Dubanchet INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorPhilippe Khadel, Philippe Khadel INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorJean Luc Voluménie, Jean Luc Voluménie INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorCatherine Bertrand Rongiéres, Catherine Bertrand Rongiéres INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this authorGeneviéve Lapprée Delage, Geneviéve Lapprée Delage INSERM, Hôpital Antoine Béclére, Clamart, FranceSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1098-0997(1997)5:2<73::AID-IDOG1>3.0.CO;2-8Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume5, Issue21997Pages 73-92 RelatedInformation

A low-molecular-weight material present in human placental supernatant (lymphocyte proliferation inhibiting factor, LPIF, or filtrate) can induce tolerance/hyporesponsivenessin vivo.We already knew from previous experiments that this material acted only on preactivated or malignant T cells, and even the malignant cells could be rescued from its action if cells were washed quickly after contact. To understand the mechanisms of its action, we have set up systems of specific stimulation. The material inhibits anti-Vβ-specific stimulation. In a mixed lymphocyte reaction if responder cell populations from a first MLR performed in the presence of LPIF are harvested, extensively washed to discard suppressor molecules, and restimulated by related or third-party lymphocytes in an H-2-incompatible combination, the response to a third-party stimulator (a primary one) is unaffected by prior exposure to the material, which nevertheless renders the population unresponsive to restimulation by the original MHC-stimulating haplotype. Cells triggered by anti-Vβ6 antibodies in the presence of LPIF are unable to undergo restimulation by the very same anti-Vβ6 MoAb, while they conserve their capacity to proliferate in a primary fashion in response to the unrelated anti-Vβ8 MoAb. When analyzed by FACS using anti-Vβ FITC-conjugated MoAbs, cells that are unresponsive or blocked in their proliferation by the action of the filtrate after anti-Vβ stimulation are still live and unexpectedly transiently hyperexpress the TcR. These findings confirm the requirement for T cell stimulation for suppression to be enacted and demonstrate that such is exerted by anergy rather than by clonal deletion, at leastin vitro.

This paper is a summary of three oral presentations, as well as the ensuing discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three members of the European Biomed group on vertical transmission of HIV (G. Chaouat, F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D. Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the Pasteur Institute, France; Irène Athanassakis, University of Crete, Greece; Eva Maria Fenyö, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such, this paper intends to be neither a review, nor an original article, but rather is an opinion paper discussing the working hypothesis of this network, as well as some of their recent results, which were presented at this meeting. The paper was issued at the request of the organizers of the meeting.

PROBLEM: Allopregnancy induces specific transient tolerance to paternal grafts, and we know that a low molecular weight material (“filtrate”) present in a human placental supernatant can do so in vitro (specific unresponsiveness) as well as in vivo, such as when preventing grafl‐versus‐host reaction (GVH) produced by A cells injected into irradiated A × B F1s recipients. We also know by studies carried out using specific anti‐Vβ‐specific stimulation as well as secondary and primary mixed lymphocyte reaction in major histocompatibility complex (MHC) only incompatible combinations that the material acts by inducing T cell anergy rather than clonal deletion. We explored the mechanism of such an anergy, which we knew was not dependent on calcium fluxes, cyclic adenosine monophosphate (cAMP) levels, or PkC by studies of protein phosphorylation. Having observed in previous studies that expression of T cell reactivity (TcR) in anergic cells was enhanced, but that the numbers of cells expressing a given Vβ after specific stimulation in the presence of a filtrate was much higher than it should be, we monitored the receptor expression by fluorescence‐activated cell sorter (FACS).METHOD OF STUDY: We used short‐term stimulation of the T‐cell‐derived Jurkat E6‐1 cells by anti‐CD3 monoclonal antibody (mAb) or phorbol myristite acetate plus calcium ionophore in the presence or absence of human placental low molecular weight suppressor factor, followed by Western blotting. Transfer on nitrocellulose filters so as to allow the revelation of the phosphorylations was realized by means of a specific antiphosphotyrosin mAb. The final revelation was obtained by chemiluminescence. Similar experiments were performed on anti‐Vβ‐stimulated BALB/c splenocytes, as well as cyproflaxin‐treated cells, which are hyper‐responsive in cell proliferation assays in the presence of the filtrate. In parallel, cells that were stimulated by a specific anti‐Vβ and were rendered specifically anergic were studied by a specific anti‐Vβ and were rendered specifically anergic were studied for other TcR expression using an FACS and both fluorescein isothiocyanate (FITC) and phycoerythrin (PE)‐labelled, related and unrelated anti‐Vβ mAbs.RESULTS: The phosphorylation of the ζ chain homodimer quantitatively defective in filtrate‐treated, anti‐Vβ6‐stimulated splenocytes as well as in Jurkatt cells. In parallel, cells from cyproflaxin‐treated Jurkatt cells were showing enhanced phosphorylation of all bands. The labelling of filtrate‐treated anti‐Vβ6‐stimulated cells by an unrelated anti‐Vβ (anti‐Vβ8) showed double expression of Vβ chains. The percentage of cells expressing this unrelated Vβ (Vβ 8) was normal.CONCLUSIONS: T cell anergy induced by a filtrate is linked to defective phosphorylation of the ζ‐chain homodimer. The abnormal percentage of cells expressing TcR after filtrate treatment might be due to adsorption by unstimulated cells of soluble TcR Vβ‐chain, possibly as a result of excess synthesis followed by membrane protease cleavage, allowing release in a soluble form of TcR Vβ‐chain nonspecifically captured by other cells.

PROBLEM: We have previously shown that supernatants from short‐term cultures of human placental explants (HPS) are immunosuppressive in vitro as well as in vivo. They contain a low M.W. factor endowed with immunoregulatories activities (Filtrate of such with a 5 kDa cut off). In this paper, we wanted to assess whether this low M.W. material accounts for most, if not all, of the immunosuppressive properties of crude HPS and begin to investigate its mode of action.RESULTS: The filtrate is active across species barrier and inhibits human and murine PHA driven lymphocyte proliferation, Mixed Lymphocyte Reaction, and Natural Killer activity as did crude HPS. It does not affect CTL lytic function at effector stage. Its cross species activity allowed us to study its effects in vivo. It corrects resorbtions in the CBA x DBA/2 murine spontaneous abortion model, and suppresses local and general GVH reactions in a model (A cells into irradiated A x B F1s) relevant to a clinical use, e.g., bone marrow transplantation.To ensure that such survival of the recipients was due to donor cells in the latter, surviving experimental animals were analysed by FACS for repopulating lymphocytes phenotype, which was indeed of donor origin.To elucidate the mechanism(s) of action of the active HPS moiety, we first tested various malignant cell lines for the minimal incubation time required for maximal lymphocyte inhibition. In the same vein, we verified that lymphocytes stimulated by PHA and simultaneously treated with filtrate were unresponsive to a second PHA challenge. The effects of the material was reversible if cells were washed out of it early enough before otherwise entering a cycle leading ultimately to cell death in vitro. Finally, we tested several second messenger pathways, none of which were modified.CONCLUSION: These data suggest that the filtrate contains an entity that represents the main, if not all, the immunosuppressive molecules present in HPS. In addition, they suggest that the material acts only on activated T cells and requires to be present early in the replication activation cycle.Altogether, the in vitro data strongly suggest that the material is acting by inducing clonal deletion in activated (T) cells.

American Journal of Reproductive ImmunologyVolume 35, Issue 4 p. 325-329 The Emerging Role of IL-10 in Pregnancy Gérard Chaouat, Corresponding Author Gérard Chaouat INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceINSERM CJF 92-09 and Department of Obstetrics and Gynecology, Hôpital Béclére, Clamart 92140, France.Search for more papers by this authorElisabeth Menu, Elisabeth Menu INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceSearch for more papers by this authorDelphine de Smedt, Delphine de Smedt INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceSearch for more papers by this authorLakshmi Khrihnan, Lakshmi Khrihnan Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this authorLin Hui, Lin Hui University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this authorAines Assal Meliani, Aines Assal Meliani Endocrinologie de l'Embryon, Jouy en Josas Cedex, FranceSearch for more papers by this authorJacques Martal, Jacques Martal Endocrinologie de l'Embryon, Jouy en Josas Cedex, FranceSearch for more papers by this authorRaj Raghupathy, Raj Raghupathy Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, KuwaitSearch for more papers by this authorThomas G. Wegmann, Thomas G. Wegmann University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this author Gérard Chaouat, Corresponding Author Gérard Chaouat INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceINSERM CJF 92-09 and Department of Obstetrics and Gynecology, Hôpital Béclére, Clamart 92140, France.Search for more papers by this authorElisabeth Menu, Elisabeth Menu INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceSearch for more papers by this authorDelphine de Smedt, Delphine de Smedt INSERM CJF 92-09 and Department of Obstetrics/Gynecology, Hospital Béclére, Clamart, FranceSearch for more papers by this authorLakshmi Khrihnan, Lakshmi Khrihnan Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this authorLin Hui, Lin Hui University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this authorAines Assal Meliani, Aines Assal Meliani Endocrinologie de l'Embryon, Jouy en Josas Cedex, FranceSearch for more papers by this authorJacques Martal, Jacques Martal Endocrinologie de l'Embryon, Jouy en Josas Cedex, FranceSearch for more papers by this authorRaj Raghupathy, Raj Raghupathy Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, KuwaitSearch for more papers by this authorThomas G. Wegmann, Thomas G. Wegmann University of Alberta, Department of Immunology, Endmonton, Alberta, CanadaSearch for more papers by this author First published: April 1996 https://doi.org/10.1111/j.1600-0897.1996.tb00488.xCitations: 32AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume35, Issue4April 1996Pages 325-329 RelatedInformation