IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells in chronic colitis

IL-2 and IL-7 share a common gamma-chain receptor and are critical for T-cell homeostasis. We aimed to clarify the reciprocal roles of IL-2 and IL-7 in the development and persistence of chronic colitis. We performed a series of adoptive transfers of IL-2(-/-) CD4(+)CD45RB(high) T cells into RAG-2(-/-) mice and assessed the role of IL-2 in the induction of IL-7R alpha on colitogenic CD4(+) T cells and the development of chronic colitis. RAG-2(-/-) mice transferred with WT but not with IL-2(-/-) CD4(+)CD45RB(high) T cells developed Th1/Th17-mediated colitis. Consistently, re-expression of IL-7R alpha was severely impaired on IL-2(-/-) but not on WT CD4(+) T cells from the transferred mice. To exclude a contribution of the preclinical autoimmunity of IL-2(-/-)mice, WT Ly5.1(+) or IL-2(-/-) Ly5.2(+) CD4(+)CD45RB(high) T cells from GFP mice previously transplanted with the same number of WT and IL-2(-/-) BM cells were transferred into RAG-2(-/-) mice. RAG-2(-/-) mice transferred with IL-2(-/-)-derived CD4(+)CD45RB(high) T cells did not develop colitis, but their splenic CD4(+) T cells changed from effector-memory to central-memory type. These results show that IL-2 is critically involved in the establishment and maintenance of IL-7-dependent colitogenic memory CD4(+)IL-7R alpha(high) T cells.