MHC class II‐independent CD25+ CD4+ CD8α β+ α β T cells attenuate CD4+ T cell‐induced transfer colitis

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Abstract
CD4+ α β T cell populations that develop in mice deficient in MHC class II (through ‘knockout’ of either the Aα, or the Aβ chain of the I-Ab molecule) comprise a major ‘single-positive’ (SP) CD4+ CD8– subset (60–90%) and a minor ‘double-positive’ (DP) CD4+ CD8α β+ subset (10–40%). Many DP T cells found in spleen, mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) express CD25, CD103 and Foxp3. Adoptive transfer of SP but not DP T cells from Aα–/– or Aβ–/– B6 mice into congenic RAG–/– hosts induces colitis. Transfer of SP T cells repopulates the host with only SP T cells; transfer of DP T cells repopulates the host with DP and SP T cells. Anti-CD25 antibody treatment of mice transplanted with DP T cells induces severe, lethal colitis; anti-CD25 antibody treatment of mice transplanted with SP T cells further aggravates the course of severe colitis. Hence, regulatory CD25+ T cells within (or developing from) the DP T cell population of MHC class II-deficient mice control the colitogenic potential of CD25– CD4+ T cells.