Ac. Jaleco et al., ANALYSIS OF LYMPHOCYTE CELL-DEATH AND APOPTOSIS IN HIV-2-INFECTED PATIENTS, Clinical and experimental immunology, 98(2), 1994, pp. 185-189
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.