The mechanism of UVB prevention of graft versus host disease.
We have previously demonstrated that Ultraviolet B (UVB) irradiation of Lewis donor bone marrow (BM) allografts prevents graft versus host disease (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 mechanism of the action of UVB irradiation was assessed by adding nonirradiated isolated cell subsets, isolated by monoclonal antibodies (Mab) to cell surface markers, to the reconstituting UVB-irradiated bone marrow inoculum. GVHD was assessed primarily on clinical grounds by observation of posture, alopecia, skin erythema, and weight loss. The addition of nonirradiated spleen cells or non-UVB-irradiated T-cell subsets (both CD4 and CD8 positive) to the otherwise UVB-irradiated donor inoculum consistently resulted in acute GVHD. In contrast, UVB irradiation of these cells resulted in full engraftment without acute GVHD. Mixed lymphocyte culture (MLC) assays confirmed responsiveness by BM transplanted hosts to third party stimulators while coculture assays failed to show any in vitro suppressor activity in the host. We conclude that UVB acts on both the T-lymphocyte and antigen presenting cell (APC) subsets to prevent acute GVHD. We also propose a model to explain tolerance based on clonal anergy produced by modified antigen presentation by UVB-irradiated APC's or by a modified response to processed antigen.
Greenfeld
J I
JI
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Chabot
J A
JA
Oluwole
S F
SF
Hardy
M A
MA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000637:transplantation; D001853:Bone Marrow / Q000528:radiation effects*; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D018920:Coculture Techniques; D004307:Dose-Response Relationship, Radiation; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006824:Hybridization, Genetic; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D014466:Ultraviolet Rays