BACKGROUND & AIMS: Although T-helper (Th) 17 and Th1 cells are involved in pathogenesis of intestinal inflammation, their developmental pathways and sufficiency to promote disease are not known; nor are the roles of CD4⁺CD25⁺ regulatory T (T(R)) cells in their development. METHODS: We performed adoptive transfer experiments to investigate the induction and suppression of colitis using naïve CD4⁺CD45RB(high) T cells and/or CD4⁺CD25⁺ T(R) cells that were obtained from retinoid-related orphan receptor gamma t (RORγt) gfp/⁺ or Ly5.1/Ly5.2 congenic mice. RESULTS: We observed 3 types of colitogenic CD4⁺ Th1 cells (interleukin [IL]-17A⁻interferon [IFN]-γ⁺): RORγt⁻ classical Th1 cells that differentiated directly from naïve T cells; RORγt⁺ Th1-like cells; and RORγt⁻ alternative Th1 cells that were terminally differentiated from RORγt⁺ cells via Th17 (IL-17A⁺IFN-γ⁻), Th17/Th1 (IL-17A⁺IFN-γ⁺), or Th1-like (IL-17A⁻IFN-γ⁺) cells. In this pathway, CD4⁺CD25⁺ T(R) cells suppress the development of not only classical Th1 cells, but also alternative Th1 cells at the transition of Th17/Th1 into alternative Th1 cells, resulting in accumulation of Th17 and Th17/Th1 cells in mice in which the development of colitis was suppressed. Furthermore, T(R) cells regulated the established balance of Th17 and Th1 cells under colitic conditions to yield a high ratio of Th17 and Th17/Th1 cells to Th1 cells in noncolitic conditions. CONCLUSIONS: Th17 and Th17/Th1 cells become colitogenic alternative Th1 cells via Th17, Th17/Th1, and Th1-like cells, independently of classical Th1 cells. T(R) cells suppress this pathway, resulting in accumulation of Th17 and Th17/Th1 cells.
BACKGROUND & AIMS: Although T-helper (Th) 17 and Th1 cells are involved in pathogenesis of intestinal inflammation, their developmental pathways and sufficiency to promote disease are not known; nor are the roles of CD4⁺CD25⁺ regulatory T (T(R)) cells in their development. METHODS: We performed adoptive transfer experiments to investigate the induction and suppression of colitis using naïve CD4⁺CD45RB(high) T cells and/or CD4⁺CD25⁺ T(R) cells that were obtained from retinoid-related orphan receptor gamma t (RORγt) gfp/⁺ or Ly5.1/Ly5.2 congenic mice. RESULTS: We observed 3 types of colitogenic CD4⁺ Th1 cells (interleukin [IL]-17A⁻interferon [IFN]-γ⁺): RORγt⁻ classical Th1 cells that differentiated directly from naïve T cells; RORγt⁺ Th1-like cells; and RORγt⁻ alternative Th1 cells that were terminally differentiated from RORγt⁺ cells via Th17 (IL-17A⁺IFN-γ⁻), Th17/Th1 (IL-17A⁺IFN-γ⁺), or Th1-like (IL-17A⁻IFN-γ⁺) cells. In this pathway, CD4⁺CD25⁺ T(R) cells suppress the development of not only classical Th1 cells, but also alternative Th1 cells at the transition of Th17/Th1 into alternative Th1 cells, resulting in accumulation of Th17 and Th17/Th1 cells in mice in which the development of colitis was suppressed. Furthermore, T(R) cells regulated the established balance of Th17 and Th1 cells under colitic conditions to yield a high ratio of Th17 and Th17/Th1 cells to Th1 cells in noncolitic conditions. CONCLUSIONS: Th17 and Th17/Th1 cells become colitogenic alternative Th1 cells via Th17, Th17/Th1, and Th1-like cells, independently of classical Th1 cells. T(R) cells suppress this pathway, resulting in accumulation of Th17 and Th17/Th1 cells.
Authors: J Shimizu; K Takai; N Fujiwara; N Arimitsu; Y Ueda; S Wakisaka; H Yoshikawa; F Kaneko; T Suzuki; N Suzuki Journal: Clin Exp Immunol Date: 2012-04 Impact factor: 4.330