Specific adaptive humoral response against a gp41 motif inhibits CD4 T-cell sensitivity to NK lysis during HIV-1 infection

Abstract

We have recently found that during HIV-1 infection, CD4 T cells overexpress a ligand of the NK activating receptor NKp44 (NKp44L) and are sensitized to NK lysis. Expression of NKp44L is triggered by a motif (3S) from the gp41, highly conserved in all HIV-1 clades. The objectives were to determine whether anti-3S antibodies were produced, could counteract 3S-CD4 interactions and were correlated to CD4 cell count and NKp44L expression in HIV-infected patients. Anti-3S antibodie production was studied in HIV-infected patients at various stages of the disease, including a longitudinal study in Asymptomatiques à Long Terme (ALT) patients. Specimens from 193 HIV-1 infected patients were examined. Anti-3S antibodies were detected by ELISA, and NKp44L expression was analysed by flow cytometry. NK cytotoxicity against CD4NKp44L cells was determined in the presence of anti-3S antibodies. Anti-3S antibodies were detected in 28.5% of HIV-infected patients. They were positively correlated to CD4 cell counts (P = 0.01) and inversely correlated to NKp44L expression (P = 0.007). Particularly, in ALT patients, a longitudinal study revealed that the CD4 cell count slope differed according to the presence or absence of anti-3S antibodies (-0.98 cells/month versus -7.48 cells/month, P > 0.001). In addition, a clear inhibition of CD4NKp44L NK lysis was observed in relationship to anti-3S antibodies titres. These results strongly suggested that anti-3S antibodies might affect disease course in inhibiting NKp44L expression and CD4 sensitivity to NK lysis. In linking specific adaptive immunity to the innate immunity induced by the 3S motif, this study may have important implications for therapeutic vaccines against AIDS.