THE MECHANISM OF UVB PREVENTION OF GRAFT-VERSUS-HOST DISEASE

We have previously demonstrated that Ultraviolet B (UVB) irradiation o f Lewis donor bone marrow (BM) allografts prevents graft versus host d isease (GVHD) in ACI recipients while allowing full engraftment. In a one-way GVHD model of parent to Lewis X BN (F1) rats, the site and mec hanism of the action of UVB irradiation was assessed by adding nonirra diated isolated cell subsets, isolated by monoclonal antibodies (Mab) to cell surface markers, to the reconstituting UVB-irradiated bone mar row inoculum. GVHD was assessed primarily on clinical grounds by obser vation of posture, alopecia, skin erythema, and weight loss. The addit ion of nonirradiated spleen cells or non-UVB-irradiated T-cell subsets (both CD4 and CD8 positive) to the otherwise UVB-irradiated donor ino culum consistently resulted in acute GVHD. In contrast, UVB irradiatio n of these cells resulted in full engraftment without acute GVHD. Mixe d lymphocyte culture (MLC) assays confirmed responsiveness by BM trans planted hosts to third party stimulators while coculture assays failed to show any in vitro suppressor activity in the host. We conclude tha t UVB acts on both the T-lymphocyte and antigen presenting cell (APC) subsets to prevent acute GVHD. We also propose a model to explain tole rance based on clonal anergy produced by modified antigen presentation by UVB-irradiated APC's or by a modified response to processed antige n. (C) 1996 Academic Press, Inc.