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


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Vieillard
Vincent
V
Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, Hôpital Pitié-Salpétrière, Paris, France. Vincent.vieillard@chups.jussieu.fr
Costagliola
Dominique
D
Simon
Anne
A
Debré
Patrice
P
D015704:CD4 Antigens / Q000276:immunology; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008137:Longitudinal Studies; D055629:Natural Cytotoxicity Triggering Receptor 2; D011971:Receptors, Immunologic / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D011971:Receptors, Immunologic; D007371:Interferon-gamma