Journal
JOURNAL OF IMMUNOLOGY
Volume 194, Issue 3, Pages 960-972Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402143
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Ministry of Health, Labor and Welfare, Japan
- Foundation of Strategic Research Projects in Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, Japan [S1311011]
- Japan Society for the Promotion of Science KAKENHI [26860760]
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24591442, 26860760, 15K15324, 26670486, 15H04879] Funding Source: KAKEN
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CD26 is associated with T cell signal transduction processes as a costimulatory molecule, and CD26(+) T cells have been suggested to be involved in the pathophysiology of diverse autoimmune diseases. Although the cellular and molecular mechanisms involved in CD26-mediated T cell activation have been extensively evaluated by our group and others, potential negative feedback mechanisms to regulate CD26-mediated activation still remain to be elucidated. In the present study, we examine the expression of inhibitory molecules induced via CD26-mediated costimulation. We show that coengagement of CD3 and CD26 induces preferential production of IL-10 in human CD4(+) T cells, mediated through NFAT and Raf-MEK-ERK pathways. A high level of early growth response 2 ( EGR2) is also induced following CD26 costimulation, possibly via NFAT and AP-1-mediated signaling, and knockdown of EGR2 leads to decreased IL-10 production. Furthermore, CD3/CD26-stimulated CD4(+) T cells clearly suppress proliferative activity and effector cytokine production of bystander T cells in an IL-10-dependent manner. Taken together, our data suggest that robust CD26 costimulatory signaling induces preferential expression of EGR2 and IL-10 as a potential mechanism for regulating CD26-mediated activation.
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