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

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

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1976-1981
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number8
DOIs
StatePublished - Feb 21 2017
Externally publishedYes

Fingerprint

Simian Immunodeficiency Virus
Virus Diseases
T-Lymphocytes
Helper-Inducer T-Lymphocytes
Germinal Center
Chemokine Receptors
Antiviral Agents
Lymph Nodes
CXC Chemokines
Th2 Cells
Macaca
Population
HIV

Keywords

  • CXCR5+CD8+ T cells
  • Follicular CD8 T cells
  • HIV
  • Lymphoid follicles
  • SIV

ASJC Scopus subject areas

  • General

Cite this

Mylvaganam, G. H., Rios, D., Abdelaal, H. M., Iyer, S., Tharp, G., Mavinger, M., ... Amara, R. R. (2017). Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. Proceedings of the National Academy of Sciences of the United States of America, 114(8), 1976-1981. https://doi.org/10.1073/pnas.1621418114

Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. / Mylvaganam, Geetha H.; Rios, Daniel; Abdelaal, Hadia M.; Iyer, Smita; Tharp, Gregory; Mavinger, Maud; Hicks, Sakeenah; Chahroudi, Ann; Ahmed, Rafi; Bosinger, Steven E.; Williams, Ifor R.; Skinner, Pamela J.; Velu, Vijayakumar; Amara, Rama R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 8, 21.02.2017, p. 1976-1981.

Research output: Contribution to journalArticle

Mylvaganam, GH, Rios, D, Abdelaal, HM, Iyer, S, Tharp, G, Mavinger, M, Hicks, S, Chahroudi, A, Ahmed, R, Bosinger, SE, Williams, IR, Skinner, PJ, Velu, V & Amara, RR 2017, 'Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 8, pp. 1976-1981. https://doi.org/10.1073/pnas.1621418114
Mylvaganam, Geetha H. ; Rios, Daniel ; Abdelaal, Hadia M. ; Iyer, Smita ; Tharp, Gregory ; Mavinger, Maud ; Hicks, Sakeenah ; Chahroudi, Ann ; Ahmed, Rafi ; Bosinger, Steven E. ; Williams, Ifor R. ; Skinner, Pamela J. ; Velu, Vijayakumar ; Amara, Rama R. / Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 8. pp. 1976-1981.
@article{58388743099e4eca8ecb036dbd30b921,
title = "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.",
keywords = "CXCR5+CD8+ T cells, Follicular CD8 T cells, HIV, Lymphoid follicles, SIV",
author = "Mylvaganam, {Geetha H.} and Daniel Rios and Abdelaal, {Hadia M.} and Smita Iyer and Gregory Tharp and Maud Mavinger and Sakeenah Hicks and Ann Chahroudi and Rafi Ahmed and Bosinger, {Steven E.} and Williams, {Ifor R.} and Skinner, {Pamela J.} and Vijayakumar Velu and Amara, {Rama R.}",
year = "2017",
month = "2",
day = "21",
doi = "10.1073/pnas.1621418114",
language = "English (US)",
volume = "114",
pages = "1976--1981",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection

AU - Mylvaganam, Geetha H.

AU - Rios, Daniel

AU - Abdelaal, Hadia M.

AU - Iyer, Smita

AU - Tharp, Gregory

AU - Mavinger, Maud

AU - Hicks, Sakeenah

AU - Chahroudi, Ann

AU - Ahmed, Rafi

AU - Bosinger, Steven E.

AU - Williams, Ifor R.

AU - Skinner, Pamela J.

AU - Velu, Vijayakumar

AU - Amara, Rama R.

PY - 2017/2/21

Y1 - 2017/2/21

N2 - 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.

AB - 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.

KW - CXCR5+CD8+ T cells

KW - Follicular CD8 T cells

KW - HIV

KW - Lymphoid follicles

KW - SIV

UR - http://www.scopus.com/inward/record.url?scp=85013335909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013335909&partnerID=8YFLogxK

U2 - 10.1073/pnas.1621418114

DO - 10.1073/pnas.1621418114

M3 - Article

C2 - 28159893

AN - SCOPUS:85013335909

VL - 114

SP - 1976

EP - 1981

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -