CD4 antigen, CD8 antigen, FOXP3+ regulatory T lymphocyte, dendritic cell, cell differentiation, spleen, transgenic mouse
Foxp3+CD25+CD4+ regulatory T cells (Treg) mediate immunological self-tolerance and suppress immune responses. A subset of dendritic cells (DCs) in the intestine is specialized to induce Treg in a TGF-β- and retinoic acid-dependent manner to allow for oral tolerance. In this study we compare two major DC subsets from mouse spleen. We find that CD8+ DEC-205/CD205+ DCs, but not the major fraction of CD8- DC inhibitory receptor-2 (DCIR2)+ DCs, induce functional Foxp3+ Treg from Foxp3- precursors in the presence of low doses of Ag but without added TGF-β. CD8 +CD205+ DCs preferentially express TGF-β, and the induction of Treg by these DCs in vitro is blocked by neutralizing Ab to TGF-β. In contrast, CD8+DCIR2+ DCs better induce Foxp3+ Treg when exogenous TGF-β is supplied. In vivo, CD8 +CD205+ DCs likewise preferentially induce Treg from adoptively transferred, Ag-specific DO11.10 RAG-/- Foxp3 -CD4+ T cells, whereas the CD8-DCIR2 + DCs better stimulate natural Foxp3+ Treg. These results indicate that a subset of DCs in spleen, a systemic lymphoid organ, is specialized to differentiate peripheral Foxp3+ Treg, in part through the endogenous formation of TGF-β. Targeting of Ag to these DCs might be useful for inducing Ag-specific Foxp3+ Treg for treatment of autoimmune diseases, transplant rejection, and allergy.
Yamazaki, S., D. Dudziak, G. F. Heidkamp, C. Fiorese, A. J. Bonito, K. Inaba, M. C. Nussenzweig, and R. M. Steinman. 2008. "CD80+CD205+ Splenic Dendritic Cells are Specialized to Induce Foxp3+ Regulatory T Cells." Journal of Immunology 181 (10): 6923-6933