PMID- 21355864 OWN - NLM STAT- MEDLINE DCOM- 20110527 LR - 20211020 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 133 IP - 1 DP - 2011 May TI - Allogeneic apoptotic thymocyte-stimulated dendritic cells expand functional regulatory T cells. PG - 123-32 LID - 10.1111/j.1365-2567.2011.03420.x [doi] AB - Dendritic cells (DCs) play an important role in the clearance of apoptotic cells. The removal of apoptotic cells leads to peripheral tolerance, although their role is still not clear. We show that the uptake of apoptotic thymocytes by DCs converts these cells into tolerogenic DCs resistant to maturation by lipopolysaccharide, modulating the production of interleukin-12 and up-regulating the expression of transforming growth factor-beta(1) latency associated peptide. We also observed that DCs pulsed with apoptotic cells in the allogeneic context were more efficient in the expansion of regulatory T cells (Tregs), and that this expansion requires contact between DCs and the T cell. The Tregs sorted from in vitro culture suppressed the proliferation of splenocytes in vitro in a specific and non-specific manner. In the in vivo model, the transfer of CD4(+) CD25(-) cells to Nude mice induced autoimmunity, with cell infiltrate found in the stomach, colon, liver and kidneys. The co-transfer of CD4(+) CD25(-) and CD4(+) CD25(+) prevented the presence of cell infiltrates in several organs and increased the total cell count in lymph nodes. Our data indicate that apoptotic cells have an important role in peripheral tolerance via induction of tolerogenic DCs and CD4(+) CD25(+) Foxp3(+) cells that present regulatory functions. CI - (c) 2011 The Authors. Immunology (c) 2011 Blackwell Publishing Ltd. FAU - da Costa, Thais Boccia AU - da Costa TB AD - Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. thais.boccia@gmail.com FAU - Sardinha, Luiz R AU - Sardinha LR FAU - Larocca, Rafael AU - Larocca R FAU - Peron, Jean P S AU - Peron JP FAU - Rizzo, Luiz V AU - Rizzo LV LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110301 PL - England TA - Immunology JT - Immunology JID - 0374672 SB - IM MH - Animals MH - Apoptosis/*immunology MH - Cell Separation MH - Dendritic Cells/*immunology MH - Female MH - Flow Cytometry MH - Immune Tolerance/*immunology MH - Lymphocyte Activation/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - T-Lymphocytes, Regulatory/*immunology PMC - PMC3088974 EDAT- 2011/03/02 06:00 MHDA- 2011/05/28 06:00 PMCR- 2012/05/01 CRDT- 2011/03/02 06:00 PHST- 2011/03/02 06:00 [entrez] PHST- 2011/03/02 06:00 [pubmed] PHST- 2011/05/28 06:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - 10.1111/j.1365-2567.2011.03420.x [doi] PST - ppublish SO - Immunology. 2011 May;133(1):123-32. doi: 10.1111/j.1365-2567.2011.03420.x. Epub 2011 Mar 1.