Spreading of HIV-specific CD8(+) T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity

Long-term non-progressors (LTNP) represent a minority of human immunodefici ency virus (HN) infected individuals characterized by stable or even increa sing CD4(+) T-cell count and by stronger immune responses against HIV than progressors. In this study, HIV-specific effector CD8(+) T cells, as detect ed by both a sensitive ex vivo enzyme-linked immunospot (ELISPOT) assay and specific major histocompatibility complex (MHC) peptide tetramers, were at a low frequency in the peripheral blood of LTNP, and recognized a lower nu mber of HIV peptides than their memory resting cell counterparts, Both fact ors may account for the lack of complete HIV clearance by LTNP, who could c ontrol the viral spread, and displayed a higher magnitude of cytotoxic T ly mphocyte (CTL) responses than progressors. By combining cell purification a nd ELISPOT assays this study demonstrates that both effector and memory res ting cells were confined to a CD8(+) population with memory CD45RO(+) pheno type, with the former being CD28(-) and the latter CD28(+) Longitudinal stu dies highlighted a relatively stable HIV specific effector repertoire, vire mia, and CD4(+) T-cell counts, which were all correlated with maintenance o f nonprogressor status, In conclusion, the analysis of HIV-specific cellula r responses in these individuals may help define clear correlates of protec tive immunity in HIV infection. Human Immunology 62, 561-576 (2001). (C) Am erican Society for Histocompatibility and Immunogenetics, 2001. Published b y Elsevier Science Inc.