Details

Autor(en) / Beteiligte

• Mylvaganam, Geetha H.
• Rios, Daniel
• Abdelaal, Hadia M.
• Iyer, Smita
• Tharp, Gregory
• Mavigner, Maud
• Hicks, Sakeenah
• Chahroudi, Ann
• Ahmed, Rafi
• Bosinger, Steven E.
• Williams, Ifor R.
• Skinner, Pamela J.
• Velu, Vijayakumar
• Amara, Rama R.

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-02, Vol.114 (8), p.1976-1981

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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+ aswell 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.