The Role of Cdcs1 and Naive T Cell Subsets in the Onset of Colitis

The interleukin-10-deficient mouse (Il10^-/-) is a suitable model for human inflammatory bowel disease research. It is known that the colitis severity in this model depends on the background strain. In a quantitative trait loci (QTL) analysis between B6.129P2/JZtm-Il10^tm1Cgn (B6-Il10^-/-) and C3Bir.129P2/JZtm-Il10^tm1Cgn (C3Bir-Il10^-/-) animals, 10 QTL, called cdcs1 (cytokine deficiency induced colitis susceptibility) to cdcs10 were identified. By breeding congenic and subcongenic strains, cdcs1 derived from C3Bir-Il10^-/- was identified as the major modifier and the cause for an adaptive hyperresponsiveness. Here we show that naive CD4⁺ T cell subsets are able to induce colitis depending on the cdcs1 region. In a transfercolitis of different naive T cell subsets (CD4⁺CD62L⁺, CD4⁺CD45^rbhigh, CD4⁺CD25^-), cells with parts of cdcs1 derived from C3Bir-Il10^-/- were able to induce much more severe colitis compared to cells derived from B6-Il10^-/-. There was no difference between the used subsets and an influence of Il-10 producing regulatory T cells could be excluded. Furthermore, we showed that the delay until the onset of colitis depends on the number of transplanted cells. A microarray analysis of naive T cells revealed 47 differently expressed probes when comparing susceptible with resistant strains. The combination of a transfercolitis model and a microarray analysis is a promising approach to identify causative genes for colitis susceptibility within cdcs1.