MHC class II-independent CD25+CD4+CD8αβ+ αβ T cells attenuate CD4+ T cell-induced transfer colitis

CD4(+) alphabeta T cell populations that develop in mice deficient in MHC class II (through 'knockout' of either the Aalpha, or the Abeta chain of the I-A(b) molecule) comprise a major 'single-positive' (SP) CD4(+) CD8(-) subset (60-90%) and a minor 'double-positive' (DP) CD4(+) CD8alphabeta(+) 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 DIP T cells from Aalpha(-/-) or Abeta(-/-) 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 DIP 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.