Regulatory CD 4 + CD 25 + cells reverse imbalances in the T cell pool of bone marrow transplanted TG e 26 mice leading to the prevention of colitis

Background and aims: Erroneous thymic selection of developing T lymphocytes may be responsible for the expansion of self reactive T cells or may contribute to the absence of regulatory T cells important in controlling peripheral inflammatory processes. Colitis in bone marrow (BM) transplanted Tge26 mice is induced by abnormally activated T cells developing in an aberrant thymic microenvironment. We investigated the protective role of regulatory CD4CD25 T cells in this model. Methods: BM from (C57BL/66CBA/J) F1 mice was transplanted into specific pathogen free Tge26 mice (BM)Tge26). Transplanted mice received no cells (control), sorted CD4CD25, or CD4CD25 cells from mesenteric lymph nodes (MLN) of normal mice. MLN cell subsets were analysed using membrane markers. Cytokine secretion of MLN cells was measured using intracellular cytokine staining and cytokine secretion in anti-CD3 stimulated cell cultures. Colitis was measured by histological scores. Results: CD4CD25 cells were reduced in the MLNs of BM)Tge26 mice. Transfer of regulatory CD4CD25 but not of CD4CD25 cells reduced the number of MLN CD4 T cells in BM)Tge26 recipients and increased the number of MLN CD8 cells, thereby normalising the CD4/CD8 ratio. CD4CD25 but not CD4CD25 cell transfer into BM)Tge26 mice reduced the number of tumour necrosis factor a CD4 cells and increased the secretion of transforming growth factor b by MLN cells. Transfer of 3610 CD4CD25 cells after BM transplantation into Tge26 mice prevented colitis whereas CD4CD25 cells had no protective effect. Conclusions: These results suggest that defective selection or induction of regulatory T cells in the abnormal thymus is responsible for the development of colitis in BM)Tge26 mice. Transfer of CD4CD25 cells can control intestinal inflammation in BM)Tge26 mice by normalising the number and function of the MLN T cell pool.