title: Regulation of HLA class II expression prevents allogeneic T-cell responses.
abstract: 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-γ) 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-γ 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.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Jaimes
authors.forename: A
authors.initials: A
authors.lastname: Seltsam
authors.forename: B
authors.initials: B
authors.lastname: Eiz-Vesper
authors.forename: R
authors.initials: R
authors.lastname: Blasczyk
authors.forename: C
authors.initials: C
authors.lastname: Figueiredo
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D006681:HLA-D Antigens; D007371:Interferon-gamma