Abstract
Purpose: A humanized anti-HLA-DR monoclonal antibody, IMMU-114 was investigated for the allogeneic immune response in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were co-cultured with inactivated self (Self) or allogeneic (Allo) stimulator PBMCs in the presence of control antibody or IMMU-114. Thymidine uptakes were measured. Phenotypic changes in PBMCs and the intracellular Th1-type cytokines, IL-2 and IFN-γ were analyzed by flow cytometry. The concentrations of IL-2 and IFN-γ in the MLR culture medium were measured. Results: Thymidine uptakes at a 1:1 responder/stimulator ratio of Allo, Allo+IMMU-114, Self, and Self+IMMU-114 were 20080.1 ± 401.2, 2004.5 ± 109.1, 1081.0 ± 116.8, and 324.1 ± 18.5 cpm, respectively (P=0.041). IMMU-114 decreased the frequencies of HLA-DR-expressing CD16+56+ NK cells (8.5 to 3.8%), CD19+ B cells (3.1 to 0.6%), and CD3+25+ activated T cells (5.6 to 4.0%). Intracellular cytokine assay and measurement of Th1-type cytokines in the MLR culture medium revealed that IMMU-114 significantly decreased the titers of IL-2 and IFN-γ. Conclusion: IMMU-114 significantly suppressed the allogeneic immune response in vitro, partly by inhibiting Th1 response.
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