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.

Comparing HIV‐1 and HIV‐2 infection: Lessons for viral immunopathogenesis

“…CD4 cell survival is significantly shortened in progressive HIV‐1 infection . Both in vivo and in vitro studies have shown that in HIV‐1 infection rates of apoptosis exceed those in healthy individuals; in HIV‐2 intermediate rates are seen, although with disease progression the proportion of apoptotic cells becomes similar to that observed in HIV‐1 infection . This lower level of apoptosis may explain the relative sparing of T lymphocytes from cell death in HIV‐2 infection.…”

Immune dysregulation in human immunodeficiency virus infection: know it, fix it, prevent it?

“…Progression of HIV‐2 infection to AIDS can occur many years after infection and is probably associated with the weakening of the immune system during ageing. In patients who develop AIDS, plasma HIV‐2 levels are comparable to those observed in HIV‐1‐infected AIDS patients, and the symptoms of the disease are undistinguishable [129–131]. The reasons for the difference in disease progression between HIV‐1 and HIV‐2 reside clearly in the different level of viral replication, but why HIV‐2 does not replicate as efficiently as HIV‐1 in humans is not clearly established [130].…”

Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections

“…However, in HIV-2 infection, the proportion of CD4+ T-cells expressing IL-2 is well preserved ( 42 ). HIV-2-infected individuals also possess a higher frequency of CD4+ T-cells capable of expressing both IFNγ and IL-2 in response to Gag-specific peptides than HIV-1 infected individuals ( 72 , 73 ). Further immunological studies revealed the presence of Gag-specific CD4+ T-cells lacking CD57 expression in HIV-2 infection ( 74 , 75 ), indicating better proliferative capacity resulting in higher number of cells in HIV-2 infected individuals ( 75 ).…”