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Immune Responses Driven by Protective Human Leukocyte Antigen Alleles From Long-term Nonprogressors Are Associated With Low HIV Reservoir in Central Memory CD4 T Cells.
MedLine Citation:
PMID:  22441653     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background. The stable immune control of human immunodeficiency virus (HIV) in long-term nonprogressors (LTNPs) with protective human leukocyte antigen (HLA) alleles raises the question of whether and how these alleles influence the immune distribution of the HIV reservoirs.Methods. Cell-associated HIV-DNA levels were quantified in blood sorted resting CD4 T-cell subsets from 8 LTNPs with and 10 without HLA-B*27 or HLA-B*57 alleles (HLA-B27/B57).Results. A remarkably lower infection level of central memory CD4 T cells (T(CM)) was an exclusive feature that distinguished the HLA-B27/B57 HIV reservoirs from the other ones. In LTNPs, T(CM) protection was correlated with preservation of T(CM) counts, which correlated positively with the magnitude of HIV Gag-specific CD8 T cells. In HLA-B27/B57 LTNPs, a lower activation level of their memory CD4 T cells was associated with lower amounts of cell HIV-DNA in each resting memory CD4 subset and were also associated with higher ratios of HIV Gag-specific CD8 T cells per infected resting CD4 T cell (effector/target [E/T]). As a result, HLA-B27/B57 E/T ratios were negatively correlated with the contribution of memory CD4 T-cell subsets to the total HIV reservoirs.Conclusions. The potent antiviral immunity governed by the protective HLA-B27/B57 alleles, by limiting T(CM) infection and pool exhaustion, are associated with a reduced T(CM) contribution to the HIV reservoir.
Authors:
Benjamin Descours; Veronique Avettand-Fenoel; Catherine Blanc; Assia Samri; Adeline Mélard; Virginie Supervie; Ioannis Theodorou; Guislaine Carcelain; Christine Rouzioux; Brigitte Autran;
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-22
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  -     ISSN:  1537-6591     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Immunity and Infection Laboratory, Pierre and Marie Curie University, INSERM UMRS 945, Pitie-Salpetriere Hospital.
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