Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated recipient immature monocyte-derived dendritic cells

Abstract

The induction of donor T-cell anergy to recipient cells for reducing GVHD could be one way of expanding donor candidates for HLA-mismatched hematopoietic SCT. The present study was designed to clarify whether recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with recipient monocyte-derived DCs (mo-DCs) irradiated with ultraviolet-C (UV-C). By irradiation of mo-DCs with UV-C, the expression of DC-associated surface phenotypes such as CD83, CD80, CD86 and CD40 was reduced and the antigen-presenting ability of UV-C-irradiated mo-DCs was clearly decreased. By co-culturing normal donor 1 lymphocytes with UV-C-irradiated donor 2 immature mo-DCs, the response of the lymphocytes to donor 2 mature mo-DCs was markedly reduced as compared with that of the lymphocytes prestimulated with non-irradiated donor 2 immature mo-DCs or UV-C-irradiated mo-DCs derived from a different individual donor 3. The present study demonstrated that recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with UV-C-irradiated recipient immature mo-DCs in hematopoietic SCT. These data suggest the applicability of donor graft cells, which have been prestimulated with UV-C-irradiated recipient immature mo-DCs, for expanding donor candidates in HLA-mismatched hematopoietic SCT.