CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens

Jacob G. Henderson; Adeleye Opejin; Andrew Jones; Cindy Gross; Daniel Hawiger

doi:10.1016/j.immuni.2015.02.010

CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens

Jacob G. Henderson, Adeleye Opejin, Andrew Jones, Cindy Gross, Daniel Hawiger

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

89 Scopus citations

Abstract

Self-reactive Tcells can escape thymic deletion and therefore some of these potentially autoaggressive Tcells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive Tcells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in Tcells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of Cd5^-/- and CD5^lo Tcells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-γ (IFN-γ) produced by bystander lymphocytes, while CD5^hi Tcells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens.

Original language	English
Pages (from-to)	471-483
Number of pages	13
Journal	Immunity
Volume	42
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2015.02.010
State	Published - Mar 17 2015

Access to Document

10.1016/j.immuni.2015.02.010

Cite this

@article{c5101f3ee5b74426a21102fdbd4929ce,

title = "CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens",

abstract = "Self-reactive Tcells can escape thymic deletion and therefore some of these potentially autoaggressive Tcells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive Tcells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in Tcells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of Cd5-/- and CD5lo Tcells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-γ (IFN-γ) produced by bystander lymphocytes, while CD5hi Tcells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens.",

author = "Henderson, {Jacob G.} and Adeleye Opejin and Andrew Jones and Cindy Gross and Daniel Hawiger",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = mar,

day = "17",

doi = "10.1016/j.immuni.2015.02.010",

language = "English",

volume = "42",

pages = "471--483",

journal = "Immunity",

issn = "1074-7613",

number = "3",

}

TY - JOUR

T1 - CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens

AU - Henderson, Jacob G.

AU - Opejin, Adeleye

AU - Jones, Andrew

AU - Gross, Cindy

AU - Hawiger, Daniel

PY - 2015/3/17

Y1 - 2015/3/17

N2 - Self-reactive Tcells can escape thymic deletion and therefore some of these potentially autoaggressive Tcells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive Tcells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in Tcells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of Cd5-/- and CD5lo Tcells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-γ (IFN-γ) produced by bystander lymphocytes, while CD5hi Tcells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens.

AB - Self-reactive Tcells can escape thymic deletion and therefore some of these potentially autoaggressive Tcells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive Tcells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in Tcells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of Cd5-/- and CD5lo Tcells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-γ (IFN-γ) produced by bystander lymphocytes, while CD5hi Tcells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens.

UR - http://www.scopus.com/inward/record.url?scp=84924988088&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2015.02.010

DO - 10.1016/j.immuni.2015.02.010

M3 - Article

C2 - 25786177

AN - SCOPUS:84924988088

SN - 1074-7613

VL - 42

SP - 471

EP - 483

JO - Immunity

JF - Immunity

IS - 3

ER -

CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens

Abstract

Access to Document

Other files and links

Fingerprint

Cite this