Document Detail


Imbalanced Production Of Cytokines By T Cells Associates With The Activation/Exhaustion Status Of Memory T Cells In Chronic HIV-1 Infection.
MedLine Citation:
PMID:  21902582     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Chronic HIV-1 infection is characterized by immune cell dysfunctions driven by chronic immune activation. Plasma HIV-1 viral load (VL) is closely correlated to disease progression and the level of immune activation. However, the mechanism by which the persistent presence of HIV-1 damages immune cells is still not fully understood. To evaluate how HIV-1 affects disruption of T cell-mediated immune responses during chronic HIV-1 infection we determined the functional profiles of T cells from subjects with chronic HIV-1 infection. We measured the capacity of PBMCs to produce 25 specific cytokines in response to non-specific T cell stimulation, and found that the capacity to produce Th-1 related cytokines (MIP-1α, MIP-1β, RANTES, IFN-γ and MIG), sIL-2R, and IL-17, but not Th-2 related cytokines, was inversely correlated to plasma VL. The capacities to produce these cytokines were interrelated; notably, IL-17 production had a strong direct correlation with production of MIP-1α, MIP-1β, RANTES, and IFN-γ. In both CD4+ and CD8+ T cells, dysfunctional production of cytokines was associated with T-cell activation (CD38 expression) and exhaustion (PD-1 and/or CTLA-4 expression) status of memory subsets. Although the capacity to produce these cytokines was recovered soon after multiple log10 reduction of plasma viral levels by antiretroviral therapy, memory CD8+ T cells remained activated and exhausted after prolonged virus suppression. Our data suggest that HIV-1 levels directly affect the ability of memory T cells to produce specifically Th1- and Th17-related cytokines during chronic HIV-1 infection.
Authors:
Kaori Nakayama; Hitomi Nakamura; Michiko Koga; Tomohiko Koibuchi; Takeshi Fujii; Toshiyuki Miura; Aikichi Iwamoto; Ai Kawana-Tachikawa
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-9
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  -     ISSN:  1931-8405     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
the Institute of Medical Science, the University of Tokyo, Division of Infectious Diseases, Tokyo, Japan; nkaori@ims.u-tokyo.ac.jp.
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