Mucosal and Systemic γδ+ T Cells Associated with Control of Simian Immunodeficiency Virus Infection.
γδ T cells act as a first line of defense against invading pathogens. However, despite their abundance in mucosal tissue, little information is available about their functionality in this compartment in the context of HIV/SIV infection. In this study, we evaluated the frequency, phenotype, and functionality of Vδ1 and Vδ2 T cells from blood, rectum, and the female reproductive tract (FRT) of rhesus macaques to determine whether these cells contribute to control of SIV infection. No alteration in the peripheral Vδ1/Vδ2 ratio in SIV-infected macaques was observed. However, CD8+and CD4+CD8+Vδ1 T cells were expanded along with upregulation of NKG2D, CD107, and granzyme B, suggesting cytotoxic function. In contrast, Vδ2 T cells showed a reduced ability to produce the inflammatory cytokine IFN-γ. In the FRT of SIV+macaques, Vδ1 and Vδ2 showed comparable levels across vaginal, ectocervical, and endocervical tissues; however, endocervical Vδ2 T cells showed higher inflammatory profiles than the two other regions. No sex difference was seen in the rectal Vδ1/Vδ2 ratio. Several peripheral Vδ1 and/or Vδ2 T cell subpopulations expressing IFN-γ and/or NKG2D were positively correlated with decreased plasma viremia. Notably, Vδ2 CD8+T cells of the endocervix were negatively correlated with chronic viremia. Overall, our results suggest that a robust Vδ1 and Vδ2 T cell response in blood and the FRT of SIV-infected macaques contribute to control of viremia.
Immune Biology of Retroviral Infection Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
Iskra
I
Tuero
Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
David
D
Venzon
Immune Biology of Retroviral Infection Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and guroffm@mail.nih.gov.
Marjorie
M
Robert-Guroff
D000818:Animals; D001775:Blood Circulation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003140:Communicable Disease Control; D003602:Cytotoxicity, Immunologic; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D009092:Mucous Membrane / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014766:Viremia
D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; D007371:Interferon-gamma