Associations of Simian Immunodeficiency Virus (SIV)-specific follicular CD8 + T cells with other follicular T cells suggest complex contributions to SIV viremia control

Mohammad Arif Rahman, Katherine M. McKinnon, Tatiana S. Karpova, David A. Ball, David J. Venzon, Wenjin Fan, Guobin Kang, Qingsheng Li, Marjorie Robert-Guroff

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Follicular CD8 + T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection. fCD8 cells of LVL animals tended to express more Gag-specific granzyme B and exhibited significantly greater killing than did HVL animals, and their cell frequencies were negatively correlated with viremia, suggesting a role in viremia control. Env- and Gag-specific IL-21 + Tfh of LVL but not HVL macaques negatively correlated with viral load, suggesting better provision of T cell help to fCD8 cells. Tfreg positively correlated with fCD8 cells in LVL animals and negatively correlated with viremia, suggesting a potential benefit of Tfreg via suppression of chronic inflammation. In contrast, in HVL macaques, Tfreg and fCD8 cell frequencies tended to be negatively correlated, and a positive correlation was seen between Tfreg number and viremia, suggesting possible dysfunction and suppression of an effective fCD8 cell immune response. Our data suggest that control of virus-infected cells in B cell follicles not only depends on fCD8 cell cytotoxicity but also on complex fCD8 cell associations with Tfh cells and Tfreg.

Original languageEnglish (US)
Pages (from-to)2714-2726
Number of pages13
JournalJournal of Immunology
Volume200
Issue number8
DOIs
StatePublished - Apr 15 2018

Fingerprint

Simian Immunodeficiency Virus
Viremia
Viral Load
T-Lymphocytes
Regulatory T-Lymphocytes
Virus Diseases
Macaca
Helper-Inducer T-Lymphocytes
Macaca mulatta
B-Lymphocytes
Granzymes
Cell Count

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Associations of Simian Immunodeficiency Virus (SIV)-specific follicular CD8 + T cells with other follicular T cells suggest complex contributions to SIV viremia control . / Rahman, Mohammad Arif; McKinnon, Katherine M.; Karpova, Tatiana S.; Ball, David A.; Venzon, David J.; Fan, Wenjin; Kang, Guobin; Li, Qingsheng; Robert-Guroff, Marjorie.

In: Journal of Immunology, Vol. 200, No. 8, 15.04.2018, p. 2714-2726.

Research output: Contribution to journalArticle

Rahman, Mohammad Arif ; McKinnon, Katherine M. ; Karpova, Tatiana S. ; Ball, David A. ; Venzon, David J. ; Fan, Wenjin ; Kang, Guobin ; Li, Qingsheng ; Robert-Guroff, Marjorie. / Associations of Simian Immunodeficiency Virus (SIV)-specific follicular CD8 + T cells with other follicular T cells suggest complex contributions to SIV viremia control In: Journal of Immunology. 2018 ; Vol. 200, No. 8. pp. 2714-2726.
@article{b6b5f5d4158e48ec80408f4187154cef,
title = "Associations of Simian Immunodeficiency Virus (SIV)-specific follicular CD8 + T cells with other follicular T cells suggest complex contributions to SIV viremia control",
abstract = "Follicular CD8 + T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection. fCD8 cells of LVL animals tended to express more Gag-specific granzyme B and exhibited significantly greater killing than did HVL animals, and their cell frequencies were negatively correlated with viremia, suggesting a role in viremia control. Env- and Gag-specific IL-21 + Tfh of LVL but not HVL macaques negatively correlated with viral load, suggesting better provision of T cell help to fCD8 cells. Tfreg positively correlated with fCD8 cells in LVL animals and negatively correlated with viremia, suggesting a potential benefit of Tfreg via suppression of chronic inflammation. In contrast, in HVL macaques, Tfreg and fCD8 cell frequencies tended to be negatively correlated, and a positive correlation was seen between Tfreg number and viremia, suggesting possible dysfunction and suppression of an effective fCD8 cell immune response. Our data suggest that control of virus-infected cells in B cell follicles not only depends on fCD8 cell cytotoxicity but also on complex fCD8 cell associations with Tfh cells and Tfreg.",
author = "Rahman, {Mohammad Arif} and McKinnon, {Katherine M.} and Karpova, {Tatiana S.} and Ball, {David A.} and Venzon, {David J.} and Wenjin Fan and Guobin Kang and Qingsheng Li and Marjorie Robert-Guroff",
year = "2018",
month = "4",
day = "15",
doi = "10.4049/jimmunol.1701403",
language = "English (US)",
volume = "200",
pages = "2714--2726",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

TY - JOUR

T1 - Associations of Simian Immunodeficiency Virus (SIV)-specific follicular CD8 + T cells with other follicular T cells suggest complex contributions to SIV viremia control

AU - Rahman, Mohammad Arif

AU - McKinnon, Katherine M.

AU - Karpova, Tatiana S.

AU - Ball, David A.

AU - Venzon, David J.

AU - Fan, Wenjin

AU - Kang, Guobin

AU - Li, Qingsheng

AU - Robert-Guroff, Marjorie

PY - 2018/4/15

Y1 - 2018/4/15

N2 - Follicular CD8 + T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection. fCD8 cells of LVL animals tended to express more Gag-specific granzyme B and exhibited significantly greater killing than did HVL animals, and their cell frequencies were negatively correlated with viremia, suggesting a role in viremia control. Env- and Gag-specific IL-21 + Tfh of LVL but not HVL macaques negatively correlated with viral load, suggesting better provision of T cell help to fCD8 cells. Tfreg positively correlated with fCD8 cells in LVL animals and negatively correlated with viremia, suggesting a potential benefit of Tfreg via suppression of chronic inflammation. In contrast, in HVL macaques, Tfreg and fCD8 cell frequencies tended to be negatively correlated, and a positive correlation was seen between Tfreg number and viremia, suggesting possible dysfunction and suppression of an effective fCD8 cell immune response. Our data suggest that control of virus-infected cells in B cell follicles not only depends on fCD8 cell cytotoxicity but also on complex fCD8 cell associations with Tfh cells and Tfreg.

AB - Follicular CD8 + T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection. fCD8 cells of LVL animals tended to express more Gag-specific granzyme B and exhibited significantly greater killing than did HVL animals, and their cell frequencies were negatively correlated with viremia, suggesting a role in viremia control. Env- and Gag-specific IL-21 + Tfh of LVL but not HVL macaques negatively correlated with viral load, suggesting better provision of T cell help to fCD8 cells. Tfreg positively correlated with fCD8 cells in LVL animals and negatively correlated with viremia, suggesting a potential benefit of Tfreg via suppression of chronic inflammation. In contrast, in HVL macaques, Tfreg and fCD8 cell frequencies tended to be negatively correlated, and a positive correlation was seen between Tfreg number and viremia, suggesting possible dysfunction and suppression of an effective fCD8 cell immune response. Our data suggest that control of virus-infected cells in B cell follicles not only depends on fCD8 cell cytotoxicity but also on complex fCD8 cell associations with Tfh cells and Tfreg.

UR - http://www.scopus.com/inward/record.url?scp=85046804670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046804670&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1701403

DO - 10.4049/jimmunol.1701403

M3 - Article

VL - 200

SP - 2714

EP - 2726

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -