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+CD45RBhigh 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+CD45RBhigh 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+CD45RBhigh 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 + CD45RBhigh 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- 7Rαhigh T cells.
ASJC Scopus subject areas
- Immunology and Allergy