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A Novel Role of CD30/CD30 Ligand Signaling in the Generation of Long-Lived Memory CD8⁺ T Cells¹

Hitoshi Nishimura^*, Toshiki Yajima^*, Hiromi Muta, Eckhard R. Podack, Kenzaburo Tani and Yasunobu Yoshikai^2,*

^* Division of Host Defense, Center for Prevention of Infectious Disease, and Division of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; and Department of Microbiology and Immunology, University of Miami, Miami, FL 33101

Memory CD8⁺ T cells can be divided into two subsets, central memory (T_CM) and effector memory (T_EM) CD8⁺ T cells. We found that CD30, a member of the TNFR-associated factor (TRAF)-linked TNFR superfamily, signaling is involved in differentiation of long-lived CD8⁺ T_CM cells following Listeria monocytogenes infection. Although CD8⁺ T_EM cells transiently accumulated in the nonlymphoid tissues of CD30 ligand (CD153^–/–) mice after infection, long-lived memory CD8⁺ T_CM cells were poorly generated in these mice. CCR7 mRNA expression was down-regulated in CD8⁺ T cells of the spleen of CD153^–/– mice in vivo and the expression was up-regulated in CD8⁺ T_EM cells by anti-CD30 mAb cross-linking in vitro. These results suggest that CD30/CD30 ligand signaling plays an important role in the generation of long-lived memory CD8⁺ T cells at least partly by triggering homing receptors for T_CM cells.

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