title: Mechanisms underlying γδ T-cell subset perturbations in SIV-infected Asian rhesus macaques.
abstract: T cells that express the γδ 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 Vδ1 and Vδ2 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 Vδ1/Vδ2 T cells occurs in blood and in several tissues; (2) γδ T cells are not infected by SIV in vivo; (3) the Vδ1/Vδ2 inversion involves expansion of Vδ1 T cells; (4) expanded Vδ1 T cells are phenotypically and functionally different from Vδ1 T cells from uninfected RMs; and (5) the stimulus underlying expansion of Vδ1 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.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Levelle D
authors.initials: LD
authors.lastname: Harris
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Carol
authors.initials: C
authors.lastname: Vinton
authors.forename: Judith A
authors.initials: JA
authors.lastname: Briant
authors.forename: Brian
authors.initials: B
authors.lastname: Tabb
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lifson
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
mesh_terms: D000818:Animals; D001208:Asia; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015759:Ionomycin / Q000494:pharmacology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D009928:Organ Specificity; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate