Mechanisms underlying ?? T-cell subset perturbations in SIV-infected Asian rhesus macaques.

ABSTRACT: T cells that express the ?? T-cell receptor, which recognize microbial or stress-induced antigens, represent a minority of blood T cells but constitute a major proportion of intraepithelial lymphocytes in the gastrointestinal mucosa. As microbial products have been shown to translocate from the gastrointestinal tract into circulation in chronically HIV/Simian immunodeficiency virus (SIV)-infected individuals, we conducted a study of V?1 and V?2 T-cell frequency, phenotype, and function in blood, spleen, lymph nodes, gastrointestinal mucosa, and bronchoalveolar lavage of uninfected and chronically SIVsmE543-infected rhesus macaques (RMs). We found: (1) SIV-associated inversion of V?1/V?2 T cells occurs in blood and in several tissues; (2) ?? T cells are not infected by SIV in vivo; (3) the V?1/V?2 inversion involves expansion of V?1 T cells; (4) expanded V?1 T cells are phenotypically and functionally different from V?1 T cells from uninfected RMs; and (5) the stimulus underlying expansion of V?1 T cells appears to be microbial translocation. These data highlight the importance of microbial translocation-induced immune activation in chronically infected individuals and provide new insights into an immune dysregulation phenomenon that is a hallmark of HIV/SIV infection. These findings may lead to novel therapeutic interventions that improve the immune responses against microbial antigens, and thus, decrease microbial translocation-induced immune activation.

SUBMITTER: Harris LD 

PROVIDER: S-EPMC2993620 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature