title: Infiltrating neutrophils induce allospecific CTL in response to immunization with apoptotic cells via MCP-1 production.
abstract: Our previous studies demonstrated that i.p. injection of late apoptotic P388 cells caused phagocytosis by macrophages and transient infiltration of neutrophils into the peritoneal cavity. As neutrophils are known to function as effectors as well as regulators in the immune response, we examined the roles of infiltrating neutrophils in alloantigen-specific CTL induction after immunization with late apoptotic P388 cells. The CTL induction and infiltration of CD8(+) T cells into the peritoneal cavity were inhibited by depletion of neutrophils by anti-Gr-1 mAb or inhibition of neutrophil infiltration by anti-MIP-2 antibody, suggesting that neutrophils are involved in CD8(+) T cell infiltration into the peritoneal cavity. It is known that MIP-1alpha, MIP-1beta, and MCP-1 are capable of attracting CD8(+) T cells and that they are produced by neutrophils. These chemokines were detected in the peritoneal cavity, and among them, MCP-1 production was reduced remarkably by suppression of neutrophil infiltration. Moreover, infiltration of CD8(+) T cells into the peritoneal cavity as well as CTL activity was clearly reduced by administering anti-MCP-1 antibody i.p. Furthermore, the CTL induction and infiltration of CD8(+) T cells in neutrophil-depleted mice were restored significantly by administering recombinant murine MCP-1 into the peritoneal cavity. These results indicate that MCP-1 appears to link infiltration of neutrophils with CTL induction.
authors.affiliation: Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Shiratsuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Iyoda
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanimoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kegai
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagata
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D007114:Immunization; D007274:Injections, Intraperitoneal; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010529:Peritoneal Cavity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000906:Antibodies; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D011993:Recombinant Fusion Proteins