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 language | English (US) |
|---|---|
| Pages (from-to) | 1976-1981 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 114 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 21 2017 |
| Externally published | Yes |
Fingerprint
Keywords
- CXCR5+CD8+ T cells
- Follicular CD8 T cells
- HIV
- Lymphoid follicles
- SIV
ASJC Scopus subject areas
- General
Cite this
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 journal › Article
}
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 -