Homeostatic proliferation of naïve CD8+ T cells depends on CD62L/L-selectin-mediated homing to peripheral LN.
Adoptive transfer of naïve 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-alphabeta(-/-) 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.
Schuster
Kerstin
K
Department of Hematology and Oncology, University Medical Center, University of Regensburg, Regensburg, Germany.
Gadiot
Jules
J
Andreesen
Reinhard
R
Mackensen
Andreas
A
Gajewski
Thomas F
TF
Blank
Christian
C
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D019041:L-Selectin / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D019041:L-Selectin