IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis

Abstract

We previously demonstrated that IL-7 is essential for the persistence of T-cell-mediated colitis, by showing that adoptive transfer of CD4 +CD45RBhigh T cells into IL-7-/- x RAG-1 +/+ mice did not induce colitis; and that intestinal IL-7 is not essential for this colitis model, by showing that IL-7-/- x RAG-1-/- mice parabiosed with colitic CD4+CD45RB high T-cell-transferred RAG-1-/- mice developed colitis. Here, we investigated the role of IL-7 in the maintenance of colitogenic CD4+ T cells by surgically separating these parabionts. Surprisingly, the separated IL-7-/- x RAG-1-/- mice were consistently diseased after separation, although no IL-7 mRNA was detected in the tissues of separated IL-7-/- x RAG-1-/- partners. CD4+ T cells isolated from the separated RAG-1-/- or IL-7-/- x RAG-1-/- mice were then transferred into new RAG-1-/- or IL-7-/- x RAG-1-/- mice. Regardless of the source of donor cells, RAG-1-/- recipients developed colitis, whereas IL-7 -/- x RAG-1-/- recipients did not. Collectively, these results demonstrate that IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ T cells rather than the maintenance of those cells in established colitic mice. They also provide a basis for the timing of IL-7/IL-7R blockade for the treatment of inflammatory bowel diseases. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.