Naturally arising CD4 CD25 regulatory T cells suppress the expansion of colitogenic CD4 CD44CD62L effector memory T cells

Kanai, T., K. Tanimoto, Y. Nemoto, R. Fujii, S. Makita, T. Totsuka, and M. Watanabe. Naturally arising CD4 CD25 regulatory T cells suppress the expansion of colitogenic CD4 CD44CD62L effector-memory T cells. Am J Physiol Gastrointest Liver Physiol 290: G1051–G1058, 2006. First published December 22, 2005; doi:10.1152/ajpgi.00429.2005.—Naturally arising CD4 CD25 regulatory T (TR) cells have been shown to prevent and cure murine T cell-mediated colitis. However, their exact mechanism of controlling colitogenic memory CD4 T cells in in vivo systems excluding the initial process of naive T cell activation and differentiation has not been examined to date. Using the colitogenic effector memory (TEM) CD4 cell-mediated colitis model induced by adoptive transfer of colitogenic CD4 CD44CD62L lamina propria (LP) T cells obtained from colitic CD4 CD45RB T cell-transferred mice, we have shown in the present study that CD4 CD25 TR cells are able not only to suppress the development of colitis, Th1 cytokine production, and the expansion of colitogenic LP CD4 TEM cells but also to expand these cells by themselves extensively in vivo. An in vitro coculture assay revealed that CD4 CD25 TR cells proliferated in the presence of IL-2-producing colitogenic LP CD4 TEM cells at the early time point (48 h after culture), followed by the acquisition of suppressive activity at the late time point (96 h after culture). Collectively, these data suggest the distinct timing of the IL-2-dependent expansion of CD4 CD25 TR cells and the their suppressive activity on colitogenic LP CD4 TEM cells.