PMID- 16952295 OWN - NLM STAT- MEDLINE DCOM- 20061121 LR - 20230124 IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 6 IP - 11 DP - 2006 Nov TI - Maturation-resistant dendritic cells induce hyporesponsiveness in alloreactive CD45RA+ and CD45RO+ T-cell populations. PG - 2580-91 AB - Dendritic cells (DCs) play a crucial role in the induction of antigen-specific immunity and tolerance. Considering in vivo application of DCs prior to human organ transplantation, a protocol to develop tolerogenic DCs that not only induce unresponsiveness in naive (CD45RA+) T cells, but also in alloreactive memory (CD45RO+) T cells is required. The present study shows that dexamethasone (Dex) alters the differentiation of human monocyte-derived DCs. DexDCs cocultured with allogeneic CD4+ T cells induced low proliferating and low IFNgamma producing T cells. This is caused by lack of both costimulation via CD28 and hampered production of a soluble factor, as well as additional active suppression via B7-H1 and IL-10. T cells primed by DexDCs demonstrated hyporesponsiveness upon restimulation with mature DCs seemingly via the induction of anergy, since these cells showed no enhanced apoptosis and only a limited suppressive capacity. Interestingly, not only cocultures of allogeneic CD45RA+, but also of CD45RO+ T cells with DexDCs rendered T-cell populations hyporesponsive to restimulation with mature DCs. The finding that also alloreactive memory T cells can be regulated supports the rationale of cell-based therapies to obtain allograft-specific tolerance in transplant recipients. FAU - Woltman, A M AU - Woltman AM AD - Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. FAU - van der Kooij, S W AU - van der Kooij SW FAU - de Fijter, J W AU - de Fijter JW FAU - van Kooten, C AU - van Kooten C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060904 PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Antigens, CD) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (Cytokines) RN - 0 (Isoantigens) RN - 130068-27-8 (Interleukin-10) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Antigens, CD/immunology MH - B7-H1 Antigen MH - Cytokines/analysis/metabolism MH - Dendritic Cells/*immunology MH - Dexamethasone/pharmacology MH - Flow Cytometry MH - Humans MH - Interleukin-10/immunology MH - Isoantigens/immunology MH - Leukocyte Common Antigens/*immunology MH - Lymphocyte Culture Test, Mixed MH - Monocytes/drug effects/immunology MH - T-Lymphocytes/*immunology EDAT- 2006/09/06 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/09/06 09:00 PHST- 2006/09/06 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/09/06 09:00 [entrez] AID - S1600-6135(22)02867-2 [pii] AID - 10.1111/j.1600-6143.2006.01520.x [doi] PST - ppublish SO - Am J Transplant. 2006 Nov;6(11):2580-91. doi: 10.1111/j.1600-6143.2006.01520.x. Epub 2006 Sep 4.