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West African populations are infected with divergent strains of human immunodeficiency virus type 2 (HIV2), some of which are closely related to simian immunodeficiency virus (SIV) and it has been postulated that the HIV2 epidemic might have arisen by cross-species spread of SIV into the human population in West Africa. To gain some insight into the possible basis for cross protection between these two closely related viruses, the T-helper responses to 15 synthetic peptides from SIV gag synthetic peptides were investigated in seven HIV2-infected subjects and in seven healthy controls. Significant reactivity to at least one of the synthetic peptides tested was found in all patients and a statistically significant correlation between CD4+ lymphocyte absolute numbers and the number of reacting peptides was observed. A marginal lymphocyte reactivity was found in two of the healthy controls studied. In conclusion, this preliminary evidence that HIV2-infected patients exhibit T-cell responses to SIV gag peptides suggests that both viruses share t-helper epitopes in the gag viral region and raises the possibility of cross protection between SIV and HIV2 which may be relevant for HIV2 vaccine research based on closely related retroviruses.

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SUMMARY The neuropeptide substance P (SP) is known to increase cell‐mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP. may represent a model for the analysis of Immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10−10 10−6) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by3H‐thymidine incorporation in peripheral blood lymphocytes from 34 HIV‐infected patients (16 asymptomtic (ASY) persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/ PGL HIV‐infected patients, SP 10−7M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A. in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide‐dependent immunoregulatory systems in HIV infection.

SUMMARY Recent evidence suggests that T cell apoptosis could be involved in the pathogenesis of HIV‐1 infection. As the progression of HIV‐2 associated disease appears to be slower than that of HIV‐1, we investigated whether there were differences in the degree of T cell death and apoptosis in peripheral blood mononuclear cell (PBMC) cultures from patients with HIV‐1 or HIV‐2 infection. PBMC from healthy controls (n = 28) and patients infected with HIV‐1 (n = 26: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL). w = 16; and AlDS‐related complex (ARC)AIDS n = 10) or HIV‐2 (n = 30: ASY/PGL, n = 16: ARC/ AIDS, n = 14) were cultured in the absence or presence of mitogens (PHA, PWM) or superantigen (SEB). After 48 h, cell death (CD) was assessed by trypan blue exclusion and in some patients programmed cell death (PCD) was quantified in flow cytometry by measuring the percentage of hypodiploid nuclei corresponding to fragmented DNA, after treating the cells with a propidium iodide hypotonic solution. HlV‐1 and HlV‐2 ARC/AIDS patients and ASY/PGL HIV‐1+ patients had significant increases in cell death percentages compared with controls, both in unstimulated and stimulated lymphocyte cultures. However, HIV‐2+ ASY/FGL patients did not exhibit significant increases of cell death in unstimutated cultures. In addition, the comparison between HIV‐l and HIV‐2 infected subjects in similar stages of disease, showed no significant differences in CD in the ARC AIDS patients, although ASY/PGL HIV‐2‐infected subjects had lower levels of CD than the HIV‐1+ ASY/PGL (3.4%± 0.6 s.e.m. versus 6.8%± M s.e.m., P < 0.01). PCD was significantly increased both in ASY/PGL (14.3%± 2.2 s.e.m., n = 8, P< 0.005) and m ARC/AIDS (25.3%± 4.5 s.e.m., n = 9, P < 0.001) HIV‐1+ patients compared with healthy controls (5.8%± l.7 s.e.m., n = 11). This contrasts with HIV‐2 infected subjects where the ASY/PGL patients (10.0%± 2.8 s.e.m., n = 6) did not differ significantly from healthy controls, although ARC/AIDS patients (27.2%± 4.2 s.e.m., n = 9. P < 0.001) had significantly increased levels of PCD. In conclusion, this is the first report describing the occurrence of spontaneous and activation‐induced lymphocyte death by apoptosis in HlV‐2 infected subjects. The lower levels of PCD in ASY/PGL HlV‐2 infected patients compared with HIV‐T patients at a similar stage justify further investigation to define whether these differences have any rote in the putative slower progression of HlV‐2 disease.