The protective mechanism of hepatitis B vaccination using surface antigen is the induction of neutralizing antibodies. Hepatitis B surface Antigen (HBsAg) has proven to be well tolerated and effective in many clinical trials 1,2.

An immunological evaluation was performed before therapy and every four months during the first year of treatment with auranofin in 6 children with juvenile chronic arthritis. The immunological tests included: IgG, IgA, IgM, IgE and "natural" antibody serum levels, CH50 of the classical and alternative complement pathways, PWM-induced IgM production in vitro, and polymorphonuclear neutrophil functions. A reduction of the in vitro IgM synthesis and in the CH50 of the classical pathway of complement, and a normalization of impaired chemotaxis, occurred in patients who presented a clinically significant improvement during auranofin treatment.

The relative distribution of T lymphocyte subsets, as defined by the monoclonal antibodies OKT, was determined by cytofluorimetric analysis in peripheral blood and in cells isolated from liver biopsies of 31 patients with chronic active hepatitis (CAH). The percentage of peripheral blood lymphocytes binding OKT8 (directed against cytotoxic/suppressor T cells) was found to be elevated in patients with HBsAg and HBeAg positive chronic active hepatitis. Patients with CAH who had seroconverted to anti-HBe, had an increased number of OKT3-positive cells in their blood, which was directed against a common T cell surface antigen, associated with a decreased number of OKT8 positive cells. Lymphocytes isolated from liver biopsies of patients with CAH presented a general increase of OKT8-positive cells associated with a decreased number of OKT4-positive (helper/inducer) T cells. It is likely that OKT8-positive cells found in liver biopsies represent cytotoxic T cells directed against either viral or liver cell determinants.

Several agents are known that can elevate cyclic AMP levels in lymphoid cells, e.g. isoproterenol, PGE1 and adenosine. We have studied the cyclic AMP increasing effect of these agents on thymocytes from mouse and man and on human peripheral T lymphocytes. In contrast to mouse thymocytes and human peripheral T lymphocytes, human thymocytes appeared to be insensitive to isoproterenol, but did respond to PGE1 and adenosine. Furthermore, the density of beta-adrenergic receptors on the cells was determined by measuring the specific binding of 3H-dihydroalprenolol. A correlation was found between the receptor density on the cells and the rise in intracellular cyclic AMP induced by isoproterenol: human thymocytes appeared to have very few beta-adrenergic receptors, in contrast to thymocytes from mouse or to T lymphocytes from human blood. We conclude that the development of beta-adrenergic receptors in T cell ontogeny is different for mice and human beings. Comparison of animal models with the situation in man should be made with caution.

Peripheral lymphocytes from individuals who had been thymectomized in adult life for myasthenia gravis (MG) or for other, nonimmunological reasons showed a moderate decrease in proliferative response capacity to several T-cell mitogens as compared to lymphocytes from normal individuals. The decrease of the response to mitogens and allogeneic lymphocytes was 20–30% within 5 years after thymectomy and about 50% more than 15 years after thymectomy. A comparable decrease in lymphocyte proliferative response capacity was found in healthy aged humans (68–97 years old). Analysis of T lymphocytes from both aged and thymectomized individuals with monoclonal (OKT) antibodies showed a similar pattern: the proportion of T lymphocytes binding OKT3 was reduced, and the OKT4/OKT8 ratio was increased. Hardly any T lymphocytes binding OKT6, OKT10, or OKT1 were found. A biochemical parameter for human T-cell differentiation, the lactate dehydrogenase (LDH) isoenzyme pattern, showed a significantly lower H/M ratio in the group of elderly people compared to young individuals. Furthermore, among patients thymectomized for MG, a significant correlation was observed between the LDH isoenzyme pattern of the T lymphocytes and the proliferative response to mitogens of these cells. In contrast, in healthy thymectomized individuals the LDH isoenzyme pattern appeared to be normal. These findings indicate that, after thymectomy or involution of the thymus, at least part of the peripheral blood T lymphocytes have properties different from those of the cells of young individuals. These cells might represent immature and/or not fully differentiated lymphocytes.

A novel subset of human blood lymphocytes was isolated by means of labelling with monoclonal antibodies and fluorescence-activated cell sorting. In normal individuals, the new subset accounts for about 2% of the blood T lymphocytes. The cells of this subset bind monoclonal antibodies specific for T lymphocytes in general [e.g. OKT3, Hu-Lyt 3(9 . 6) and Leu-22] and they also form E rosettes. However, no binding is seen with monoclonal antibodies to T-lymphocyte subsets (OKT4, OKT8, Leu-2A and Leu-3A). Moreover, the lymphocytes of this new subset express neither Ia antigens nor membrane immunoglobulins. They do not bind OKM1, an antibody against cells of the myelomonocytic lineage that also reacts with natural killer cells, nor do they bind OKT6 or OKT10, specific for thymocyte antigens. The cells have a high specific gravity, a thymocyte-like pattern of lactate dehydrogenase isoenzymes and do not contain terminal deoxynucleotidyl transferase. Although these lymphocytes are viable, also after culture in vitro, and can be stored in liquid nitrogen, they are inert in all functional systems tested: they neither proliferate upon stimulation with mitogens or allogeneic cells, nor do they display suppressor or natural killer cell activity. A patient who was successfully reconstituted by bone marrow transplantation for severe combined immunodeficiency, was found to contain an abnormally high (25%--30%) fraction of these OKT3 positive, OKT4 and OKT8 negative cells among his circulating T lymphocytes.

Although more than 30 families with adenosine deaminase (ADA) deficiency and severe combined immunodeficiency (SCID) have been described the precise mechanism through which the deficiency of ADA produces immunodeficiency is still unknown. Only in the past few years the investigations on purine metabolites in some patients with ADA deficiency and SCID1-4 have enhanced our understanding of the immune dysfunction. Here we describe the metabolic findings observed in a 10 week-old girl with SCID and ADA deficiency. The patient was hospitalized for respiratory distress and mucocutaneous Candidiasis. Severe impairment of both cellular and humoral immunity was found. The ADA activity was measured5 in a red cell hemolysate and was found to be absent. The ADA level in the mother's red cells was 0.07Δ E293 nm/hour/mg hemoglobin (normal x= 0.231±0.080) and in the father's red cells 0.14. The patient worsened rapidly and died 3 weeks later. Autopsy confirmed the diagnosis of SCID with presence of Candida in the lung, kidney, heart and brain.

Normal human E rosette-forming, Fc-IgG receptor-bearing cells (so-called T gamma cells) were separated into two functionally different subpopulations. Both subpopulations bind the monoclonal antibody OKM1 (directed against an antigen present also on monocytes and granulocytes). The first subpopulation accounts for about 70% of the total T gamma cell population, does not bind OKT3 (a monoclonal antibody directed against an antigen present on most T lymphocytes), and displays strong killer (K) cell and natural killer (NK) cell activity. The second subpopulation accounts for about 30% of the total T gamma population, binds both OKT3 and OKM1 (confirmed with a double-labeling assay), and displays low K and NK cell activity. Each subset contained less than 10% null cells. Comparison of T gamma cell populations obtained by adherence to a monolayer of IgG-coated human erythrocytes or by rosette formation with these cells revealed that pure T gamma cells with normal killer cell and natural killer cell activity were best obtained with the monolayer technique. Comparison of the enzymic and functional profile of T gamma cells, monocytes and granulocytes, as well as changes during culture of these cells in vitro, failed to indicate a relationship between T gamma cells and cells of the myelomonocytic lineage.

In patients with severe combined immunodeficiency, who have been successfully treated by bone-marrow transplantation, the occurrence of split take has been well documented: whereas myelomonocytic hemopoietic cell lines remain of host origin, the T-lymphoid compartment is of donor origin, while the B-lymphoid compartment may be either of host or of donor origin. We have studied the T gamma cells of two patients, successfully treated by bone-marrow transplantation from donors of the opposite sex, with respect to the sex-chromosome pattern, the binding of OKM1 and OKT3 monoclonal antibody and their K and NK activity. All T gamma cells of both patients were found to be of donor origin. These T gamma cells contained two serologically distinct subpopulations, one OKM1+ OKT3+, the other OKM1+ OKT3-, as was also found in normals. However, the ratio between these two subpopulations is 0.6 in normals, whereas these patients revealed a ratio of 3.0. Furthermore, the patients' T gamma cells displayed a strongly reduced K and NK activity (+/- 30% of normal). We concluded that at least part of the OKM1+ OKT3+ and of the OKM1+ OKT3- T gamma cells are derived from other than the myelomonocytic lineage, presumably from the lymphocytic lineage. The origin of the K and NK active T gamma cells, however, cannot be conclusively determined from these experiments. These findings also imply that the antigen detected by OKM1 should obviously no longer be regarded as exclusively present on myelomonocytic cells.

The composition of nuclear proteins from human thymocytes and T lymphocytes from peripheral blood was analyzed. Total thymocytes and total peripheral blood T lymphocytes differed markedly in non-histone chromatin proteins (both phosphorylated and non-phosphorylated), but did not differ in histones. When the cells were separated according to density, T-lymphocyte fractions with a close specific gravity showed restricted differences in non-histone chromatin patterns.