Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection.
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.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.|Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Geetha H
GH
Mylvaganam
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
Daniel
D
Rios
Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108.|Department of Microbiology and Immunology, Zagazig University, Zagazig, Egypt 44519.
Hadia M
HM
Abdelaal
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Smita
S
Iyer
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Gregory
G
Tharp
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
Maud
M
Mavigner
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Sakeenah
S
Hicks
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
Ann
A
Chahroudi
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; ramara@emory.edu vvelu@emory.edu rahmed@emory.edu.|Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Rafi
R
Ahmed
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Steven E
SE
Bosinger
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
Ifor R
IR
Williams
Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108.
Pamela J
PJ
Skinner
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.
Vijayakumar
V
Velu
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; ramara@emory.edu vvelu@emory.edu rahmed@emory.edu.|Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Rama R
0000-0002-6309-6797
RR
Amara
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002908:Chronic Disease; D018858:Germinal Center / Q000166:cytology*; D008253:Macaca mulatta; D008297:Male; D054380:Receptors, CXCR5 / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
D054380:Receptors, CXCR5
CXCR5+CD8+ T cells; HIV; SIV; follicular CD8 T cells; lymphoid follicles