Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

Brodie Miles; Shannon M. Miller; Joy M. Folkvord; Abigail Kimball; Mastooreh Chamanian; Amie L. Meditz; Tessa Arends; Martin D. McCarter; David N. Levy; Eva G. Rakasz; Pamela J. Skinner; Elizabeth Connick

doi:10.1038/ncomms9608

Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

Brodie Miles, Shannon M. Miller, Joy M. Folkvord, Abigail Kimball, Mastooreh Chamanian, Amie L. Meditz, Tessa Arends, Martin D. McCarter, David N. Levy, Eva G. Rakasz, Pamela J. Skinner, Elizabeth Connick

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (T_FR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (T_FH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on T_FR number and function. We find that T_FR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, T_FR exhibit elevated regulatory phenotypes and impair T_FH functions during HIV infection. Thus, T_FR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.

Original language	English (US)
Article number	8608
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9608
State	Published - Oct 20 2015

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms9608

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@article{cdc4db9ba5134ee891e1bba111c55884,

title = "Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection",

abstract = "Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.",

author = "Brodie Miles and Miller, {Shannon M.} and Folkvord, {Joy M.} and Abigail Kimball and Mastooreh Chamanian and Meditz, {Amie L.} and Tessa Arends and McCarter, {Martin D.} and Levy, {David N.} and Rakasz, {Eva G.} and Skinner, {Pamela J.} and Elizabeth Connick",

note = "Funding Information: We thank Mario Santiago for valuable discussions and comments. We also thank David Watkins and Nancy Wilson for sharing reagents and animal specimens. MVC (cat #11580), bicyclam (cat # 8128) and RAL (cat # 11680) were obtained through the NIH AIDS reagent program. This work was funded by NIH/NIAID grants R01 AI096966 to E.C. and P.J.S., R01 AI078783A to D.N.L., 5T32AI007447-22 T32 to B.M., T32 5T32AI007447 to M.C., T32 AI007405 to S.M.M. NIH/NHLBI PHS grant HL103286 to T.A., and the Wisconsin National Primate Research Center (WNPRC) P51OD011106. Cell sorting was performed by the University of Colorado Cancer Flow Cytometry Shared Resource, which is supported by the Cancer Center Support Grant P30CA046934 and the Skin Diseases Research Cores Grant P30AR057212. The funding source played no role in experimental design or data analysis. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = oct,

day = "20",

doi = "10.1038/ncomms9608",

language = "English (US)",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

AU - Miles, Brodie

AU - Miller, Shannon M.

AU - Folkvord, Joy M.

AU - Kimball, Abigail

AU - Chamanian, Mastooreh

AU - Meditz, Amie L.

AU - Arends, Tessa

AU - McCarter, Martin D.

AU - Levy, David N.

AU - Rakasz, Eva G.

AU - Skinner, Pamela J.

AU - Connick, Elizabeth

N1 - Funding Information: We thank Mario Santiago for valuable discussions and comments. We also thank David Watkins and Nancy Wilson for sharing reagents and animal specimens. MVC (cat #11580), bicyclam (cat # 8128) and RAL (cat # 11680) were obtained through the NIH AIDS reagent program. This work was funded by NIH/NIAID grants R01 AI096966 to E.C. and P.J.S., R01 AI078783A to D.N.L., 5T32AI007447-22 T32 to B.M., T32 5T32AI007447 to M.C., T32 AI007405 to S.M.M. NIH/NHLBI PHS grant HL103286 to T.A., and the Wisconsin National Primate Research Center (WNPRC) P51OD011106. Cell sorting was performed by the University of Colorado Cancer Flow Cytometry Shared Resource, which is supported by the Cancer Center Support Grant P30CA046934 and the Skin Diseases Research Cores Grant P30AR057212. The funding source played no role in experimental design or data analysis. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/10/20

Y1 - 2015/10/20

N2 - Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.

AB - Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.

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JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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ER -

Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

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