Analysis of lymphocyte cell death and apoptosis in HIV-2-infected patients

Abstract

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.