Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0606399 on November 9, 2006

Published online before print November 9, 2006
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(Journal of Leukocyte Biology. 2007;81:412-420.)
© 2007 by Society for Leukocyte Biology

Infiltrating neutrophils induce allospecific CTL in response to immunization with apoptotic cells via MCP-1 production

Yoshiko Shiratsuchi, Takuya Iyoda, Naoko Tanimoto, Daisuke Kegai, Kisaburo Nagata and Yoshiro Kobayashi1

Division of Molecular Medicine, Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Japan

1 Correspondence: Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. E-mail: yoshiro{at}biomol.sci.toho-u.ac.jp

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-1{alpha}, MIP-1ß, 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.

Key Words: peritoneal cavity • inflammation • chemokines • immune response




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