Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 11, Pages 2981-2990Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200939330
Keywords
Cell homing; Homeostasis; T cells
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [768/1-1, 1-2]
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Adoptive transfer of naive CD8(+) T cells into lymphopenic recipients results both in spontaneous proliferation and in partial activation of T cells, a phenomenon termed homeostatic proliferation (HP). HP of CD8(+) T cells is dependent on host IL-7, IL-15, and MHC-class I and has been shown to prevent T-cell tolerance, reverse T-cell anergy and support T-cell-mediated tumor control in vivo. However, the initial anatomic site of HP is still under debate. Since we observed that the earliest detectable HP occurs within LN and that T cells undergoing HP retain a CD62L bright phenotype, we investigated the functional role of CD62L for this process. We found that CD62L-expression on T cells is required for optimal HP and HP was impaired in lymphotoxin-alpha beta(-/-) mice, indicating the necessity for intact host secondary lymphoid organ structures. Use of the LN egression inhibitor FTY720 indicated that LN structures were pivotal to yield homeostatically proliferated T cells detected in other compartments. Consistent with these results, HP-supported control of MC57-SIY tumors depended on CD62L. Our data indicate a critical role for CD62L and LN homing for the process of HP, which has implications for adoptive immunotherapy approaches of cancer.
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