期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 10, 页码 3015-3025出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201444701
关键词
Homeostatic proliferation; Memory CD4(+) T cells; OX40; Th17
类别
资金
- Ministry of Education, Science, Sports, and Culture of Japan
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Cell Science Research Foundation
- Hiromi Medical Research Foundation
- Japan Rheumatism Foundation
- Grants-in-Aid for Scientific Research [24390118, 14J06157] Funding Source: KAKEN
T-cell homeostasis preserves the numbers, the diversity and functional competence of different T-cell subsets that are required for adaptive immunity. Naive CD4(+) T (T-N) cells are maintained in the periphery via the common.-chain family cytokine IL-7 and weak antigenic signals. However, it is not clear how memory CD4(+) T-cell subsets are maintained in the periphery and which factors are responsible for the maintenance. To examine the homeostatic mechanisms, CFSE-labeled CD4(+) CD44(high)CD62L(low) effector memory T (T-EM) cells were transferred into sublethally-irradiated syngeneic C57BL/6 mice, and the systemic cell proliferative responses, which can be divided distinctively into fast and slow proliferations, were assessed by CFSE dye dilution. We found that the fast homeostatic proliferation of T-EM cells was strictly regulated by both antigen and OX40 costimulatory signals and that the slow proliferation was dependent on IL-7. The simultaneous blockade of both OX40 and IL-7 signaling completely inhibited the both fast and slow proliferation. The antigen-and OX40-dependent fast proliferation preferentially expanded IL-17-producing helper T cells (Th17 cells). Thus, OX40 and IL-7 play synergistic, but distinct roles in the homeostatic proliferation of CD4(+) T-EM cells.
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