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P-Selectin Glycoprotein Ligand-1 Negatively Regulates T-Cell Immune Responses¹

Masanori Matsumoto,^* Masayuki Miyasaka,^* and Takako Hirata^2*

*Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine and World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; and Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Cell surface sialomucins often act as antiadhesive molecules by virtue of their extended structure and negative charge. CD43 is one such sialomucin, expressed on most leukocytes. P-selectin glycoprotein ligand-1 (PSGL-1) is another sialomucin expressed by leukocytes. It serves as a major selectin ligand, but no antiadhesive role for it has been described. In this study, we showed that PSGL-1-deficient T cells, like CD43-deficient T cells, exhibited increased adhesion and proliferation compared with wild-type cells. The loss of both PSGL-1 and CD43 led to a further increase in T cell adhesion and proliferation. The reexpression of full-length PSGL-1 or CD43 in double-deficient CD4⁺ T cells reversed their increased adhesion and proliferation phenotype. Using chimeric constructs of human CD8 and either PSGL-1 or CD43, we demonstrated that the intracellular domain of PSGL-1 or CD43 is required for suppressing proliferation but not adhesion. Furthermore, in a mouse model of inflammatory bowel disease induced by the adoptive transfer of naive T cells into RAG-deficient hosts, a PSGL-1 deficiency exacerbated the development of inflammation. These results reveal a novel regulatory role for PSGL-1 in T cell adhesion and proliferation and suggest that PSGL-1 negatively regulates T cell immune responses in vivo.

Correspondence: ² Address correspondence and reprint requests to Dr. Takako Hirata, Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan. E-mail address: thirata{at}ak.med.kyoto-u.ac.jp

¹ This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan; a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; and a Grant of Long-Range Research Initiative (LRI) by the Japan Chemical Industry Association (JCIA).