Heterogeneity in HIV suppression by CD8 T cells from HIV controllers: association with Gag-specific CD8 T cell responses.
"HIV controllers" (HICs) are rare individuals in whom HIV-1 plasma viral load remains undetectable without antiretroviral treatment. This spontaneous viral control in HICs is usually associated to strong functional HIV-specific CD8(+) T cell responses. Accordingly, we have recently shown that CD8(+) T cells from HICs strongly suppress ex vivo HIV-1 infection of autologous CD4(+) T cells, suggesting a crucial role of this response in vivo. Knowledge of the mechanisms underlying the CD8(+) T cell antiviral activity might help to develop effective T cell-based vaccines. In the present work, we further characterized the HIV-suppressive capacity of CD8(+) T cells in 19 HICs. CD8(+) T cells from 14 of the 19 HICs showed strong HIV-suppressive capacity ex vivo. This capacity was stable over time and was partially effective even on other primate lentiviruses. HIV-suppressive capacity of CD8(+) T cells correlated strongly with the frequency of HIV-specific CD8(+) T cells, and in particular of Gag-specific CD8(+) T cells. We also identified five HICs who had weak HIV-suppressive CD8(+) T cell capacities and HIV-specific CD8(+) T cell responses. Among these five HICs, at least three had highly in vitro replicative viruses, suggesting that the control of viremia in these patients is not due to replication-defective viruses. These results, on the one hand, suggest the importance of Gag responses in the antiviral potency of CD8(+) T cells from HICs and, on the other hand, propose that other host mechanisms may contribute to restraining HIV infection in HICs.
Sáez-Cirión
Asier
A
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Sinet
Martine
M
Shin
So Youn
SY
Urrutia
Alejandra
A
Versmisse
Pierre
P
Lacabaratz
Christine
C
Boufassa
Faroudy
F
Avettand-Fènoël
Véronique
V
Rouzioux
Christine
C
Delfraissy
Jean-François
JF
Barré-Sinoussi
Françoise
F
Lambotte
Olivier
O
Venet
Alain
A
Pancino
Gianfranco
G
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018740:Genetic Heterogeneity; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014779:Virus Replication
D015683:Gene Products, gag; D007371:Interferon-gamma