|
|
Nonlytic Suppressive Activity against Different Biological Variants of HIV-1 by CD8+ T Lymphocytes from Exposed Uninfected Individuals L. FURCI*, P. LOVERRO, L. LOPALCO, M. SINNONE, A. LAZZARIN, and P. LUSSO. S. Raffaele Sci. Inst., Milan, Italy Many individuals who remain uninfected despite multiple unprotected sexual encounters with HIV-infected partners (EU) display evidence of HIV-specific immunity, including antigen-driven T helper cell-mediated cytokine production and cytotoxicity induced by HIV early proteins. We have recently shown, in an Italian cohort of EU, a cellular immune response, of the T-helper type, directed toward the Env protein of HIV-1. Env-specific CD4+ T cells produced high levels of ß-chemokines and were powerful suppressors of CXCR4-negative HIV-1 strains (C5). We explored the role of an unconventional form of anti-HIV immune activity, mediated by CD8+ lymphocytes, which results in the inhibition of virus replication in infected cells. This response does not require HLA compatibility and does not involve cell killing. Although ß-chemokines are important components of such activity, it is evident that other factors are involved because CXCR4-tropic HIV-1 strains can also be suppressed, albeit less consistently than the CXCR4-negative strains. We studied CD8+ cell non-cytotoxic suppression of HIV-1 replication in a cohort of 15 sexually-exposed uninfected subjects, in parallel to a group of 12 unexposed control subjects and 23 HIV-seropositive subjects. Our results indicate that: (a) CD8+ T lymphocytes isolated from EU individuals strongly inhibit HIV replication in vitro in a non-lytic, HLA-unrestricted manner; (b) the HIV-suppressive activity is directed against R5, X4- and dualtropic (R5X4) HIV strains; (c) CD8+ T cells exert their inhibitory activity in the absence of exogenous stimuli, reflecting a status of T-cell activation and functional competence in vivo. These results suggest that non-lytic, CD8+ T-cell-mediated mechanisms of control of HIV replication may play an important role in the protective immunity of EU individuals. Key Words: CD8 lymphocytes, HIV suppression, protective immunity |
|
© 7th
Conference on Retroviruses and Opportunistic Infections, |