CD80+CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells

Sayuri Yamazaki, Diana Dudziak, Gordon Heidkamp

OAI: oai:digitalcommons.rockefeller.edu:steinman-publications-1202

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-?- 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-?. CD8 +CD205+ DCs preferentially express TGF-?, and the induction of Treg by these DCs in vitro is blocked by neutralizing Ab to TGF-?. In contrast, CD8+DCIR2+ DCs better induce Foxp3+ Treg when exogenous TGF-? 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-?. Targeting of Ag to these DCs might be useful for inducing Ag-specific Foxp3+ Treg for treatment of autoimmune diseases, transplant rejection, and allergy.

CD4 antigen CD8 antigen FOXP3+ regulatory T lymphocyte dendritic cell Cell Differentiation Spleen Transgenic mouse