The Expanding Role of TNF-Receptor Super Family Member CD40 (tnfrsf5) in Autoimmune Disease: Focus on Th40 Cells

Author(s): Gisela Vaitaitis, Dan Waid, David H. Wagner Jr..

Journal Name: Current Immunology Reviews

Volume 6 , Issue 2 , 2010

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Abstract:

CD40 is a member of the TNF receptor super family (tnfrsf) thats role in autoimmunity has been long established. Predominantly studies focus on CD40 as an antigen presenting cell receptor. We and others determined that CD40 acts as a functional receptor on T cells. In fact CD40 is a co-stimulus for T cells potentially precluding the CD28 – B7 costimulation axis. CD40+ T cells (Th40) are highly pathogenic - transferring type 1 diabetes (T1D) to SCID mice. The number and percentage of Th40 cells increases concurrently with insulitits through diabetes onset. An important finding was that blocking CD40 – CD154 interactions prevents T1D onset, and reestablishes homeostatic balance between Th40 cells and traditional, naturally occurring regulatory T cells (Tregs). We discovered a distinct dysregulation between Th40 cells and Tregs during autoimmunity. The actual number and function of Tregs in NOD mice, the model of T1D, is in fact normal. The percentage of Tregs is skewed to appear abnormally low. We determined that Th40 cells over time in NOD mice radically outpace Tregs in number and percentage. Mechanistically Th40 cells have lower levels of the death inducing Fas molecule and are highly resistant to cell death. Th40 cells are capable of producing Th1 cytokines including IFNγ and TNFα but also can produce IL-17A, demonstrating a pro-inflammatory phenotype.

Keywords: CD40, TNFR-super family, autoimmunity, Th40, inflammation

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2010
Page: [130 - 136]
Pages: 7
DOI: 10.2174/157339510791111673
Price: $58

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