P-selectin glycoprotein ligand-1 negatively regulates T-cell immune responses.
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.
Matsumoto
Masanori
M
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.
Miyasaka
Masayuki
M
Hirata
Takako
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D051917:Leukosialin / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016827:CD8 Antigens; D051917:Leukosialin; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein