Journal
IMMUNITY
Volume 29, Issue 6, Pages 934-946Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.10.009
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Funding
- Dutch Cancer Society [NKI 2003-2859]
- European Community [MUGEN LSHG-CT-2005-005203]
- Swiss National Science Foundation
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Steady-state dendritic cells (DCs) maintain peripheral T cell tolerance, whereas mature DCs generate immunity. CD70 is a costimulatory ligand acquired upon DC maturation. To determine its impact on T cell fate, we have generated mice that constitutively express CD70 in conventional DCs (cDCs). In these mice, naive CD4(+) and CD8(+) T cells spontaneously convert into effector cells. Administration of peptide without adjuvant, which is ordinarily tolerogenic, elicited tumor-eradicating CD8(+) T cell responses and robust CD4(+) T cell-independent memory. CD70 was also constitutively expressed in cDCs that inducibly present viral epitopes. In this case, tolerance induction was prevented as well. The antigen-presenting DCs generated protective immunity to virus infection and broke a pre-existing state of CD8(+) T cell tolerance. Thus, the sole expression of CD70 by otherwise immature cDCs sufficed to convert CD8(+) T cell tolerance into immunity, defining the importance of CD27-CD70 interactions at the interface between T cell and DC.
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