Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity

Joyce Wei, P'ng Loke, Xingxing Zang, James P. Allison

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system-infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.

Original languageEnglish (US)
Pages (from-to)1683-1694
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number18
DOIs
StatePublished - Aug 1 2011

Fingerprint

Autoimmunity
Wild Animals
T-Lymphocytes
Islets of Langerhans
Peripheral Tolerance
Th17 Cells
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Disease Progression
Central Nervous System
Proteins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity. / Wei, Joyce; Loke, P'ng; Zang, Xingxing; Allison, James P.

In: Journal of Experimental Medicine, Vol. 208, No. 18, 01.08.2011, p. 1683-1694.

Research output: Contribution to journalArticle

Wei, Joyce ; Loke, P'ng ; Zang, Xingxing ; Allison, James P. / Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity. In: Journal of Experimental Medicine. 2011 ; Vol. 208, No. 18. pp. 1683-1694.
@article{de3b798299dd41cf93e16393f3c46ef7,
title = "Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity",
abstract = "B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system-infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.",
author = "Joyce Wei and P'ng Loke and Xingxing Zang and Allison, {James P.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1084/jem.20100639",
language = "English (US)",
volume = "208",
pages = "1683--1694",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "18",

}

TY - JOUR

T1 - Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity

AU - Wei, Joyce

AU - Loke, P'ng

AU - Zang, Xingxing

AU - Allison, James P.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system-infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.

AB - B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system-infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.

UR - http://www.scopus.com/inward/record.url?scp=79961147546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961147546&partnerID=8YFLogxK

U2 - 10.1084/jem.20100639

DO - 10.1084/jem.20100639

M3 - Article

C2 - 21727190

AN - SCOPUS:79961147546

VL - 208

SP - 1683

EP - 1694

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 18

ER -