PMID- 21155720 OWN - NLM STAT- MEDLINE DCOM- 20110526 LR - 20101215 IS - 1399-0039 (Electronic) IS - 0001-2815 (Linking) VI - 77 IP - 1 DP - 2011 Jan TI - Regulation of HLA class II expression prevents allogeneic T-cell responses. PG - 36-44 LID - 10.1111/j.1399-0039.2010.01576.x [doi] AB - Human leukocyte antigen (HLA) class II molecules are polymorphic heterodimers that present peptides to CD4+ T-cells. The HLA-DM molecule contributes to assemble HLA class II-peptide complexes. We investigated the effect of silencing either HLA-DR or HLA-DM expression in the allogeneic T-cell responses. The delivery of HLA-DR- or HLA-DM-specific short hairpin RNAs (shRNAs) in a monocytic cell line caused a decrease by up to 85% and 75% at the respective mRNA level. Allogeneic T-cells stimulated with HLA-DM-silenced monocytes decreased to 30% granzyme B mRNA and interferon gamma (IFN-gamma) production in comparison with T-cells stimulated with monocytes expressing a non-specific shRNA. By contrast, HLA-DR-silenced monocytes did not induce proliferation, up-regulation of granzyme B mRNA levels or high IFN-gamma secretion by allogeneic T-cells vs HLA-DR expressing cells. Direct targeting of HLA-DR expression prevented more efficiently an allogeneic T-cell response in comparison with the knockdown of the expression of HLA-DM molecules. Silencing the expression of HLA-DR molecules might contribute to the development of new allogeneic cell-based therapeutic approaches. CI - (c) 2010 John Wiley & Sons A/S. FAU - Jaimes, Y AU - Jaimes Y AD - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany. FAU - Seltsam, A AU - Seltsam A FAU - Eiz-Vesper, B AU - Eiz-Vesper B FAU - Blasczyk, R AU - Blasczyk R FAU - Figueiredo, C AU - Figueiredo C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (HLA-D Antigens) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Blotting, Western MH - Cell Line, Tumor MH - Cell Proliferation MH - Flow Cytometry MH - *Gene Expression Regulation MH - Gene Silencing MH - HLA-D Antigens/genetics/*immunology MH - Humans MH - Interferon-gamma/metabolism MH - T-Lymphocytes/cytology/*immunology EDAT- 2010/12/16 06:00 MHDA- 2011/05/27 06:00 CRDT- 2010/12/16 06:00 PHST- 2010/12/16 06:00 [entrez] PHST- 2010/12/16 06:00 [pubmed] PHST- 2011/05/27 06:00 [medline] AID - 10.1111/j.1399-0039.2010.01576.x [doi] PST - ppublish SO - Tissue Antigens. 2011 Jan;77(1):36-44. doi: 10.1111/j.1399-0039.2010.01576.x.