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

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.

CD4+ T Cell Differentiation in Chronic Viral Infections: The Tfh Perspective

“…As has been observed in LCMV, CXCR5+ virus-specific CD8 + T cells have also recently been shown to increase in both HIV and in SIV infections 62,109 , suggesting that the upregulation of a follicular program in both CD4 + and CD8 + T cells is conserved and that mice may be used to model these processes. Animal modeling in HIV has already helped to describe ways in which the increased Tfh response may be altered by chronic infection.…”

Compromised steady‐state germinal center activity with age in nonhuman primates

“…Follicular CD8 (fCD8) T cells, potential regulators of follicular dynamics (Miles et al, ), accumulate during chronic viral infections (Ferrando‐Martinez et al, ) (Mylvaganam et al, ). Therefore, we sought to investigate the steady‐state dynamics of fCD8 T cells with respect to age.…”

“…, accumulate during chronic viral infections(Ferrando-Martinez et al, 2018) (Mylvaganam et al, 2017). Therefore, we sought to investigate the steady-state dynamics of fCD8 T cells with respect to age.…”

Whole body MRI of the non-human primate using a clinical 3T scanner: initial experiences

“…CD4+ T cells are a primary target of HIV and CD4 cell depletion is a major factor in the pathogenesis of HIV infection (42). Also, CD8+ T cells play a critical role in controlling HIV viremia and reducing overall numbers of HIV-infected cells in approaches to eradicate HIV (43,44). Due to their roles in the process of the adaptive immune system, tracking these T cells in vivo will play a critical role in drug discovery and modern vaccine development (45,46).…”