Mechanisms underlying γδ T-cell subset perturbations in SIV-infected Asian rhesus macaques
Autor: | Jeffrey D. Lifson, Carol L. Vinton, Judith A. Briant, Vanessa M. Hirsch, David Price, Kristin Ladell, Jason M. Brenchley, Levelle D. Harris, Jacob D. Estes, Brian Tabb, Nichole R. Klatt |
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Rok vydání: | 2010 |
Předmět: |
CD4-Positive T-Lymphocytes
Asia Immunology Simian Acquired Immunodeficiency Syndrome Spleen Biology medicine.disease_cause Biochemistry Lymphocyte Depletion Interleukin 21 Immune system Antigen T-Lymphocyte Subsets medicine Animals Cytotoxic T cell Immunobiology Ionomycin Receptors Antigen T-Cell gamma-delta Cell Biology Hematology Immune dysregulation Simian immunodeficiency virus Macaca mulatta Virology Phenotype medicine.anatomical_structure Organ Specificity Tetradecanoylphorbol Acetate Intraepithelial lymphocyte Simian Immunodeficiency Virus |
Zdroj: | Blood. 116:4148-4157 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood-2010-05-283549 |
Popis: | 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 im-mune activation. |
Databáze: | OpenAIRE |
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