CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes

Deborah J. Lenschow, Kevan C. Herold, Lesley Rhee, Bina Patel, Ann Koons, Hui Yu Qin, Elaine Fuchs, Bhagarith Singh, Craig B. Thompson, Jeffrey A. Bluestone

Research output: Contribution to journalArticlepeer-review

324 Scopus citations

Abstract

CD28 ligation delivers a costimulatory signal important in T cell activation. This study demonstrates that the disruption of the CD28/B7 pathway early in the non-obese diabetic mouse strain, using CD28(-/-) and CTLA4lg transgenic mice, promoted the development and progression of spontaneous autoimmune diabetes. Functional analyses of T cells isolated from GD28-deficient mice demonstrated that the CAD-specific T cells produced enhanced Th1-type cytokines (IL-2 and IFNγ) and diminished Th2-type cytokine, IL-4. Moreover, there was a significant decrease in serum levels of anti-GAD antibodies of the IgG1 isotype consistent with a profound suppression of Th2-type responses in these animals. Thus, the early differentiation of naive diabetogenic T cells into the Th2 subset is dependent upon CD28 signaling and extends our understanding of the importance of Th1/Th2 balance in the regulation of this spontaneous autoimmune disease.

Original languageEnglish
Pages (from-to)285-293
Number of pages9
JournalImmunity
Volume5
Issue number3
DOIs
StatePublished - Sep 1996

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