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 immunodeficiency virus (HIV) infected individuals characterized by stable or even increasing CD4 + T-cell count and by stronger immune responses against HIV than progressors. In this study, HIV-specific effector CD8 + T cells, as detecte...

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Bibliographic Details
Published in:Human immunology 2001-06, Vol.62 (6), p.561-576
Main Authors: Propato, Antonella, Schiaffella, Enrico, Vicenzi, Elisa, Francavilla, Vittorio, Baloni, Letizia, Paroli, Marino, Finocchi, Luigi, Tanigaki, Nobuyuki, Ghezzi, Silvia, Ferrara, Rosa, Chesnut, Robert, Livingston, Brian, Sette, Alessandro, Paganelli, Roberto, Aiuti, Fernando, Poli, Guido, Barnaba, Vincenzo
Format: Article
Language:English
Subjects:
Adult
CD8 + T lymphocytes
CD8-Positive T-Lymphocytes - immunology
ELISPOT
Female
HIV Infections - immunology
HIV Infections - virology
HIV type-1
HIV-1 - immunology
HLA-A2 Antigen - immunology
HLA-A2.1 tetramers
HLA-A3 Antigen - immunology
Humans
Immunologic Memory
long-term nonprogressors
Longitudinal Studies
Male
Middle Aged
Peptides - immunology
Survivors
T-Lymphocytes, Cytotoxic - immunology
Viral Load
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Summary:Long-term non-progressors (LTNP) represent a minority of human immunodeficiency virus (HIV) infected individuals characterized by stable or even increasing CD4 + T-cell count and by stronger immune responses against HIV than progressors. In this study, HIV-specific effector CD8 + T cells, as detected 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 number of HIV peptides than their memory resting cell counterparts. Both factors may account for the lack of complete HIV clearance by LTNP, who could control the viral spread, and displayed a higher magnitude of cytotoxic T lymphocyte (CTL) responses than progressors. By combining cell purification and ELISPOT assays this study demonstrates that both effector and memory resting cells were confined to a CD8 + population with memory CD45RO + phenotype, with the former being CD28 − and the latter CD28 +. Longitudinal studies highlighted a relatively stable HIV-specific effector repertoire, viremia, and CD4 + T-cell counts, which were all correlated with maintenance of nonprogressor status. In conclusion, the analysis of HIV-specific cellular responses in these individuals may help define clear correlates of protective immunity in HIV infection.
ISSN:0198-8859
1879-1166
DOI:10.1016/S0198-8859(01)00245-2