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

IL-2 and IL-7 share a common γ-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-7Rα 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-7Rα 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- 7Rα^high T cells.