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Distinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes
Journal article   Peer reviewed

Distinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes

Govindarajan Rajagopalan, Ashutosh K Mangalam, Moon M Sen, Yogish C Kudva and Chella S David
Autoimmunity, Vol.40(7), pp.489-496
01/01/2007
DOI: 10.1080/08916930701649836
PMID: 17966038

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Abstract

The strong MHC class II association in human as well as murine Type 1 diabetes (T1D) suggests a central role for CD4 + T cells in the disease pathogenesis. Nonetheless, CD8 + T cells also play a role in the pathogenic process. We describe how CD4 + or CD8 + T cells can contribute differentially to the pathogenesis of T1D using the HLA-DQ8 transgenic mouse models. HLA-DQ8 transgenic mice expressing the costimulatory molecule, B7.1 (RIP.B7.1), or the proinflammatory cytokine, TNF-α (RIP.TNF) or both (RIP.B7.RIP.TNF) under the control of rat insulin promoter (RIP) were used. Our observations indicate that in the RIP-B7 model, CD4 + T cells were absolutely required for diabetes to occur. However, when CD8 + T cells were also present, the incidence of diabetes increased. On the other hand, in the RIP-TNF model, CD8 + T cells were absolutely required for diabetes to occur. Interestingly, when CD4 + T cells were also present, the incidence of diabetes decreased. In the RIP-B7.RIP-TNF double transgenic mouse model, either CD4 + or CD8 + T cells were sufficient to precipitate diabetes in 100% of the animals. Thus, the relative roles of CD4 + or CD8 + T cells in the pathogenesis of T1D are possibly determined by the local inflammatory stimuli.
 HLA-DQ8 MHC NOD transgenic mice

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