IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells in chronic colitis.
IL-2 and IL-7 share a common gamma-chain receptor and are critical for T-cell homeostasis. We aimed to clarify the reciprocal roles of IL-2 and IL-7 in the development and persistence of chronic colitis. We performed a series of adoptive transfers of IL-2(-/-) CD4(+)CD45RB(high) T cells into RAG-2(-/-) mice and assessed the role of IL-2 in the induction of IL-7R alpha on colitogenic CD4(+) T cells and the development of chronic colitis. RAG-2(-/-) mice transferred with WT but not with IL-2(-/-) CD4(+)CD45RB(high) T cells developed Th1/Th17-mediated colitis. Consistently, re-expression of IL-7R alpha was severely impaired on IL-2(-/-) but not on WT CD4(+) T cells from the transferred mice. To exclude a contribution of the preclinical autoimmunity of IL-2(-/-)mice, WT Ly5.1(+) or IL-2(-/-) Ly5.2(+) CD4(+)CD45RB(high) T cells from GFP mice previously transplanted with the same number of WT and IL-2(-/-) BM cells were transferred into RAG-2(-/-) mice. RAG-2(-/-) mice transferred with IL-2(-/-)-derived CD4(+)CD45RB(high) T cells did not develop colitis, but their splenic CD4(+) T cells changed from effector-memory to central-memory type. These results show that IL-2 is critically involved in the establishment and maintenance of IL-7-dependent colitogenic memory CD4(+)IL-7R alpha(high) T cells.
Kameyama
Kaori
K
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Nemoto
Yasuhiro
Y
Kanai
Takanori
T
Shinohara
Tamako
T
Okamoto
Ryuichi
R
Tsuchiya
Kiichiro
K
Nakamura
Tetsuya
T
Sakamoto
Naoya
N
Totsuka
Teruji
T
Hibi
Toshifumi
T
Watanabe
Mamoru
M
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000096:biosynthesis; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015851:Interleukin-7 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018183:Transplantation Chimera
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D020381:Interleukin-17; D007376:Interleukin-2; D015851:Interleukin-7; C499308:Rag2 protein, mouse; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain