Susceptibility to HIV infection and AIDS in Italian haemophiliacs is HLA associated.

We compared the frequencies of HLA antigens in two matched groups of 31 HIV-seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981-85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs.

Histocompatibility in Italian couples with recurrent spontaneous abortions of unknown origin and with normal fertility.

We investigated HLA antigen and haplotype frequencies in 47 couples with primary recurrent abortions of unknown origin, in 65 fertile couples, and in a control panel of 98 males and 92 females. A significant increase of HLA-B17 was found in abortion couples in comparison with fertile couples. No difference between abortion and control fertile couples was observed regarding HLA sharing.

MLC-specific suppressor T lymphocytes in man. I. Their induction in vitro by soluble HLA-DR antigens.

Human T lymphocytes precultured for 36 hr in the presence of soluble HLA-DR antigens suppress the MLR response of autologous peripheral blood lymphocytes to allogeneic stimulating cells. The suppression is DR antigen-specific in that it appears that the MLR stimulating cell donor and the soluble suppressor-inducing antigen must share DR specificities. The soluble DR antigens were fractionated from the sera of normal donors using QAE-Sephadex chromatography and CNBr-activated Sepharose immunoadsorption. Similarly prepared HLA-A and -B antigens failed to induce suppressive activity. The suppressive activity of DR-antigen cultured T cells is resistant to mitomycin C treatment and, further, the antigen specificity is maintained with or without mitomycin C treatment. The kinetics of suppressor cell induction as well as the kinetics of suppression in the test MLR cultures are presented. The implications of these results are discussed.

Serum factors influencing spontaneous rosette formation by lymphocytes of pregnant women.

The effect of sera from pregnant women on the percentage of spontaneous rosette-forming peripheral lymphocytes was investigated. Pregnancy lymphocytes displayed a significantly lower capacity to bind SRBC than control male lymphocytes. However, after an exhaustive washing, it was possible to demonstrate a significant increase of spontaneous rosettes formed by pregnancy lymphocytes. It was found that the incubation of pregnancy-washed lymphocytes with pregnancy but not homologous male serum restored to depressed levels the values of rosette-forming peripheral lymphocytes. This blocking activity was significantly higher with autologous serum than homologous pregnancy serum. Control lymphocytes were unaffected both by washing and by incubation with pregnancy sera. The blocking activity was found in the same ion-exchange chromatography fraction of pregnancy serum where paternal HLA antigens could be demonstrated, and was reproduced by a soluble HLA preparation from the husband's lymphocytes.

Expression of Fc and complement receptors on T lymphocytes activated in vitro by phytohaemagglutinin (PHA).

In this work T-enriched lymphocyte populations (obtained from Ig-anti-Ig-Degalancoated columns) were studied for their surface markers, especially for Fc and complement receptors, before and after a pulse-PHA-stimulation. It has been demonstrated that activated T lymphocytes express on their surface both of these markers in high percentage. The hypothesis is discussed that B and T lymphocytes differ only with regard to the presence of surface immunoglobulins or the ability of forming spontaneous rosettes. On the contrary the other surface markers may probably be expressed when needed functionally by the cells.

Effect of ageing on surface IgG of human peripheral lymphocytes.

An increase in the percentage of IgG bearing peripheral blood lymphocytes is observed in aged subjects as compared with young ones. Such a finding is probably due to the presence, in 'aged' sera, of a higher concentration of immune complexes, bound to lymphocytes through their Fc or Complement receptors.

Histocompatibility antigens and effects of neuroactive drugs on phytohaemagglutinin stimulation of lymphocytes in vitro.

The effects of a psychopharmacological agent, sulpiride, and of some neuromediators, dopamine, norepinephrine and propranolol, on the uptake of 3H-thymidine by lymphocytes stimulated in vitro with phytohaemagglutinin (PHA) were studied. The lymphoctes were obtained from two populations of subjects, one with HLA-AL CRAG antigens of the HLA-SD series and one without. We found that the presence of the CRAG antigens in the lymphocytes led in the presence of the various drugs to behaviour different from what was seen when the antigens were not present. When the two groups were pooled, PHA lymphocytes activation was inhibited by dopamine, sulpiride, and propranolol and was not effected by norepinephrine.

HL-A antigens in serum from bone marrow harvested for diagnostic purposes.

Tissue typing employing the lymphocytotoxicity micro-assay was performed by introducing in the system approximately 15% of autologous or homologous ultra-centrifuged blood serum, both of peripheral and bone marrow source. As a rule, the pattern of reactivity was unaffected by peripheral blood serum, whereas the cytotoxicity was nearly always inhibited by autologous bone marrow blood serum or by homologous one from donors sharing the inhibited HL-A specificities with the donors of lymphocytes. These results suggest that at least in these patients HL-A antigens are present in bone marrow blood serum at a concentration which is definitely higher than in peripheral blood.