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

Veterinary and Biomedical Sciences

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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

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© 2015 Macmillan Publishers Limited.

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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.",

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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

PY - 2015/10/20

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

Abstract

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