Mucosal and Systemic γδ+ T Cells Associated with Control of Simian Immunodeficiency Virus Infection

J Immunol. 2016 Dec 15;197(12):4686-4695. doi: 10.4049/jimmunol.1600579. Epub 2016 Nov 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Blood Circulation
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Communicable Disease Control
  • Cytotoxicity, Immunologic
  • Female
  • Genitalia, Female / immunology*
  • Genitalia, Female / virology
  • HIV Infections / immunology*
  • Humans
  • Immunity, Mucosal
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Macaca mulatta
  • Male
  • Mucous Membrane / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / physiology*
  • Viremia

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • T-cell receptor Vdelta2, human
  • Interferon-gamma