Thymocyte/splenocyte-derived CD4+CD25+Treg stimulated by anti-CD200R2 derived dendritic cells suppress mixed leukocyte cultures and skin graft rejection. Export

@article{citeulike:1016797, abstract = {BACKGROUND: CD200 delivers immunoregulatory signals following engagement of its receptor, CD200R. A family of CD200Rs (CD200R1-4) has been described. Spleen expresses cell surface CD200R1, while bone marrow shows predominantly expression of cell surface CD200R2/R3. We showed that dendritic cell precursors (DCp) cultured with anti-CD200R2/3 develop the capacity to induce CD4(+)CD25(+) regulatory T cells (Treg) from peripheral lymphocytes. We now characterize DCs involved in induction of antigen-specific Treg from thymocytes or peripheral T cells, and the properties of Treg cells maintained in long-term culture. METHODS: Bone marrow DCp (C3H or BL/6 origin) were cultured for 8 days with GMCSF, IL-4 and anti-CD200R2, or with CD200Fc and a previously described peptide inhibitor of CD200R1 to allow preferential engagement of non-CD200R1 receptors by CD200. Mixed leukocyte cultures (MLCs) were initiated with allogeneic responder lymphocytes/thymocytes (BL/6 or C3H) and mitomycin-c treated DCs to induce Treg. Treg cells were maintained by reculture with DCs derived in the same manner and IL-2, cloned at limiting dilution, and tested for their ability to suppress MLCs and skin graft rejection in vivo. RESULTS: Foxp3(+) CD4(+)CD25(+) Treg were derived from 60-hr thymocyte and splenocyte T cell cultures using both DC populations. Cloned C3H Treg (Foxp3(+)) suppressed both C3H anti-BL/6 reactivity in a fresh MLC and rejection of BL/6 skin allografts in C3H recipients; the converse was true for BL/6 Treg. CONCLUSIONS: We conclude that CD200 triggering of bone-marrow DCs in the absence of CD200R1 engagement induces CD4(+)CD25(+) Treg, and these cloned antigen-specific Treg may have clinical utility.}, address = {Transplant Research Division, Toronto Hospital, University Health Network, Ontario, Canada. reg.gorczynski@utoronto.ca}, author = {Gorczynski, R. M.}, citeulike-article-id = {1016797}, citeulike-linkout-0 = {http://dx.doi.org/10.1097/01.tp.0000214984.65520.50}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16612280}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16612280}, day = {15}, doi = {10.1097/01.tp.0000214984.65520.50}, issn = {0041-1337}, journal = {Transplantation}, keywords = {cd200, cd200r, treg}, month = {April}, number = {7}, pages = {1027--1034}, posted-at = {2006-12-27 12:38:39}, priority = {3}, title = {Thymocyte/splenocyte-derived CD4+CD25+Treg stimulated by anti-CD200R2 derived dendritic cells suppress mixed leukocyte cultures and skin graft rejection.}, url = {http://dx.doi.org/10.1097/01.tp.0000214984.65520.50}, volume = {81}, year = {2006} }

TY - JOUR ID - citeulike:1016797 L3 - citeulike-article-id:1016797 N2 - BACKGROUND: CD200 delivers immunoregulatory signals following engagement of its receptor, CD200R. A family of CD200Rs (CD200R1-4) has been described. Spleen expresses cell surface CD200R1, while bone marrow shows predominantly expression of cell surface CD200R2/R3. We showed that dendritic cell precursors (DCp) cultured with anti-CD200R2/3 develop the capacity to induce CD4(+)CD25(+) regulatory T cells (Treg) from peripheral lymphocytes. We now characterize DCs involved in induction of antigen-specific Treg from thymocytes or peripheral T cells, and the properties of Treg cells maintained in long-term culture. METHODS: Bone marrow DCp (C3H or BL/6 origin) were cultured for 8 days with GMCSF, IL-4 and anti-CD200R2, or with CD200Fc and a previously described peptide inhibitor of CD200R1 to allow preferential engagement of non-CD200R1 receptors by CD200. Mixed leukocyte cultures (MLCs) were initiated with allogeneic responder lymphocytes/thymocytes (BL/6 or C3H) and mitomycin-c treated DCs to induce Treg. Treg cells were maintained by reculture with DCs derived in the same manner and IL-2, cloned at limiting dilution, and tested for their ability to suppress MLCs and skin graft rejection in vivo. RESULTS: Foxp3(+) CD4(+)CD25(+) Treg were derived from 60-hr thymocyte and splenocyte T cell cultures using both DC populations. Cloned C3H Treg (Foxp3(+)) suppressed both C3H anti-BL/6 reactivity in a fresh MLC and rejection of BL/6 skin allografts in C3H recipients; the converse was true for BL/6 Treg. CONCLUSIONS: We conclude that CD200 triggering of bone-marrow DCs in the absence of CD200R1 engagement induces CD4(+)CD25(+) Treg, and these cloned antigen-specific Treg may have clinical utility. IS - 7 JF - Transplantation SN - 0041-1337 AD - Transplant Research Division, Toronto Hospital, University Health Network, Ontario, Canada. reg.gorczynski@utoronto.ca EP - 1034 TI - Thymocyte/splenocyte-derived CD4+CD25+Treg stimulated by anti-CD200R2 derived dendritic cells suppress mixed leukocyte cultures and skin graft rejection. VL - 81 SP - 1027 KW - cd200 KW - cd200r KW - treg AU - Gorczynski, RM PY - 2006/04/15/ UR - http://dx.doi.org/10.1097/01.tp.0000214984.65520.50 ER -