Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis

• Published in: European journal of immunology 2010-09, Vol.40 (9), p.2409-2422
• Main Authors: Mikami, Yohei, Kanai, Takanori, Sujino, Tomohisa, Ono, Yuichi, Hayashi, Atsushi, Okazawa, Akira, Kamada, Nobuhiko, Matsuoka, Katsuyoshi, Hisamatsu, Tadakazu, Okamoto, Susumu, Takaishi, Hiromasa, Inoue, Nagamu, Ogata, Haruhiko, Hibi, Toshifumi
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD4 Antigens - biosynthesis; Cell Communication - immunology; Colitis - immunology; Colitis - pathology; Colitis - physiopathology; Cytokines; Disease Models, Animal; DNA-Binding Proteins - genetics; Humans; Inflammation; Inflammatory bowel disease; Inflammatory Bowel Diseases - immunology; Interleukin-10 - genetics; Interleukin-17 - secretion; Leukocyte Common Antigens - biosynthesis; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucosa; Mucous Membrane - immunology; Mucous Membrane - pathology; Parabiosis; Rodent; Rodents; T cells; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040379

Th17 cells and Th1 cells coordinate to play a critical role in the formation of inflammatory bowel diseases. To examine how Th17 and Th1 cells are regulated at inflammatory sites, we used Th1-dominant CD4⁺CD45RBhigh T cell-transferred RAG-2⁻/⁻ and Th1/Th17-mixed IL-10⁻/⁻ mice. Interestingly, not only did colitic RAG-2⁻/⁻ mice that were parabiosed with WT mice show significant amelioration of colitis, but amelioration of disease was also observed in those parabiosed with colitic IL-10⁻/⁻ mice. To assess the interference between Th1 and Th17 colitogenic T cells, we co-transferred colitogenic CD4⁺ T cells from the lamina propria (LP) of CD4⁺CD45RBhigh T cell-transferred RAG-2⁻/⁻ mice and IL-10⁻/⁻ mice into RAG-2⁻/⁻ mice. Surprisingly, the co-transferred RAG-2⁻/⁻ mice showed a vast cellular infiltration of LP CD4⁺ T cells similar to that seen in RAG-2⁻/⁻ mice re-transferred with the cells from colitic RAG-2⁻/⁻ mice alone, but the co-transferred RAG-2⁻/⁻ mice did not have the wasting symptoms, which are also absent in RAG-2⁻/⁻ mice transferred with cells from colitic IL-10⁻/⁻ mice alone. Furthermore, the percentages of Th1 and Th17 cells originating from IL-10⁻/⁻ mice and those of Th1 cells originating from colitic RAG-2⁻/⁻ mice were all significantly decreased in the co-transferred mice as compared with the singly-transferred paired RAG-2⁻/⁻ mice, suggesting that Th1 and Th17 cells are in competition, and that their orchestration results in a merged clinical phenotype of the two types of murine colitis.