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A costimulatory function for T cell CD40
Journal article   Peer reviewed

A costimulatory function for T cell CD40

Melissa E Munroe and Gail A Bishop
The Journal of immunology (1950), Vol.178(2), pp.671-682
01/15/2007
DOI: 10.4049/jimmunol.178.2.671
PMID: 17202327

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Abstract

CD40 plays a significant role in the pathogenesis of inflammation and autoimmunity. B cell CD40 directly activates cells, which can result in autoantibody production. T cells can also express CD40, with an increased frequency and amount of expression seen in CD4(+) T lymphocytes of autoimmune mice, including T cells from mice with collagen-induced arthritis. However, the mechanisms of T cell CD40 function have not been clearly defined. To test the hypothesis that CD40 can serve as a costimulatory molecule on T lymphocytes, CD40(+) T cells from collagen-induced arthritis mice were examined in parallel with mouse and human T cell lines transfected with CD40. CD40 served as effectively as CD28 in costimulating TCR-mediated activation, including induction of kinase and transcription factor activities and production of cytokines. An additional enhancement was seen when both CD40 and CD28 signals were combined with AgR stimulation. These findings reveal potent biologic functions for T cell CD40 and suggest an additional means for amplification of autoimmune responses.
Signal Transduction Cell Line Humans Mice, Inbred C57BL Arthritis, Experimental - immunology CD3 Complex - metabolism Transcription Factor AP-1 - metabolism Arthritis, Experimental - metabolism CD28 Antigens - metabolism Lymphocyte Activation - immunology Animals CD40 Antigens - metabolism T-Lymphocytes - metabolism Female T-Lymphocytes - immunology CD40 Antigens - genetics Mice CD40 Antigens - immunology Cytokines - biosynthesis

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