ANALYSIS OF LYMPHOCYTE CELL-DEATH AND APOPTOSIS IN HIV-2-INFECTED PATIENTS

Recent evidence suggests that T cell apoptosis could be involved in th e pathogenesis of HIV-1 infection. As the progression of HIV-2 associa ted disease appears to be slower than that of HIV-1, we investigated w hether there were differences in the degree of T cell death and apopto sis in peripheral blood mononuclear cell (PBMC) cultures from patients with HIV-1 or HIV-2 infection. PBMC from healthy controls (n = 28) an d patients infected with HIV-1 (n = 26: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL), n = 16; and AIDS-related complex (A RC)/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 sup erantigen (SEB). After 48 h, cell death (CD) was assessed by trypan bl ue exclusion and in some patients programmed cell death (PCD) was quan tified in flow cytometry by measuring the percentage of hypodiploid nu clei corresponding to fragmented DNA, after treating the cells with a propidium iodide hypotonic solution. HIV-1 and HIV-2 ARC/AIDS patients and ASY/PGL HIV-1(+) patients had significant increases in cell death percentages compared with controls, both in unstimulated and stimulat ed lymphocyte cultures. However, HIV-2(+) ASY/PGL patients did not exh ibit significant increases of cell death in unstimulated cultures. In addition, the comparison between HIV-1 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 lo wer levels of CD than the HIV-1(+) ASY/PGL (3.4% +/- 0.6 s.e.m. versus 6.8% +/- 1.1 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 in ARC/AIDS (2 5.3% +/- 4.5 s.e.m., n = 9, P < 0.001) HIV-1(+) patients compared with healthy controls (5.8% +/- 1.7 s.e.m., n = 11). This contrasts with H IV-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 signif icantly increased levels of PCD. In conclusion, this is the first repo rt describing the occurrence of spontaneous and activation-induced lym phocyte death by apoptosis in HIV-2 infected subjects. The lower level s of PCD in ASY/PGL HIV-2 infected patients compared with HIV-1(+) pat ients at a similar stage justify further investigation to define wheth er these differences have any role in the putative slower progression of HIV-2 disease.