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

Abstract

CD4+ αβ 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+ CD8αβ + 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. © 2004 WILEY-VCH Verlag GmbH & Co.