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Proc Natl Acad Sci U S A. 2017 Feb 21;114(8):1976-1981. doi: 10.1073/pnas.1621418114. Epub 2017 Feb 3.

Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection.

Author information

1
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
2
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
3
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
4
Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108.
5
Department of Microbiology and Immunology, Zagazig University, Zagazig, Egypt 44519.
6
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
7
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; ramara@emory.edu vvelu@emory.edu rahmed@emory.edu.
8
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; ramara@emory.edu vvelu@emory.edu rahmed@emory.edu.

Abstract

A significant challenge to HIV eradication is the elimination of viral reservoirs in germinal center (GC) T follicular helper (Tfh) cells. However, GCs are considered to be immune privileged for antiviral CD8 T cells. Here, we show a population of simian immunodeficiency virus (SIV)-specific CD8 T cells express CXCR5 (C-X-C chemokine receptor type 5, a chemokine receptor required for homing to GCs) and expand in lymph nodes (LNs) following pathogenic SIV infection in a cohort of vaccinated macaques. This expansion was greater in animals that exhibited superior control of SIV. The CXCR5+ SIV-specific CD8 T cells demonstrated enhanced polyfunctionality, restricted expansion of antigen-pulsed Tfh cells in vitro, and possessed a unique gene expression pattern related to Tfh and Th2 cells. The increase in CXCR5+ CD8 T cells was associated with the presence of higher frequencies of SIV-specific CD8 T cells in the GC. Following TCR-driven stimulation in vitro, CXCR5+ but not CXCR5- CD8 T cells generated both CXCR5+ as well as CXCR5- cells. However, the addition of TGF-β to CXCR5- CD8 T cells induced a population of CXCR5+ CD8 T cells, suggesting that this cytokine may be important in modulating these CXCR5+ CD8 T cells in vivo. Thus, CXCR5+ CD8 T cells represent a unique subset of antiviral CD8 T cells that expand in LNs during chronic SIV infection and may play a significant role in the control of pathogenic SIV infection.

KEYWORDS:

CXCR5+CD8+ T cells; HIV; SIV; follicular CD8 T cells; lymphoid follicles

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