PT  - JOURNAL ARTICLE
AU  - Yamazaki, Sayuri
AU  - Dudziak, Diana
AU  - Heidkamp, Gordon F.
AU  - Fiorese, Christopher
AU  - Bonito, Anthony J.
AU  - Inaba, Kayo
AU  - Nussenzweig, Michel C.
AU  - Steinman, Ralph M.
TI  - CD8<sup>+</sup>CD205<sup>+</sup> Splenic Dendritic Cells Are Specialized to Induce Foxp3<sup>+</sup> Regulatory T Cells
AID  - 10.4049/jimmunol.181.10.6923
DP  - 2008 Nov 15
TA  - The Journal of Immunology
PG  - 6923--6933
VI  - 181
IP  - 10
4099  - http://www.jimmunol.org/content/181/10/6923.short
4100  - http://www.jimmunol.org/content/181/10/6923.full
SO  - J. Immunol.2008 Nov 15; 181
AB  - 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.