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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Feb 21 2017|
Bibliographical noteFunding Information:
We thank the Yerkes Division of Research Resources and veterinary staff for animal care and procedures, the Emory Flow Cytometry core for cell sorting, Emory Center For Aids Research Virology Core for VL assays, and the NIH AIDS Research and Reference Reagent Program for the provision of peptides. This work was supported by National Institutes of Health Grants R36 AI112787, P01 AI88575, and U19 AI109633 (to R.R.A.) and AI096966 (to P.J.S.); Yerkes National Primate Research Center Base Grant P51 RR00165; and Emory Center for AIDS Research Grant P30 AI050409.
- CXCR5+CD8+ T cells
- Follicular CD8 T cells
- Lymphoid follicles