UVB irradiation of human-derived peripheral blood lymphocytes induces apoptosis but not T-cell anergy: additive effects with various immunosuppressive agents.
UVB irradiation of bone marrow or pancreatic islets has been shown to prevent GVHD and to induce transplant tolerance in experimental animal models. To clarify the underlying mechanism(s) responsible for these UVB effects we have examined in vitro cell function following UVB irradiation using LDA, FACS analysis, and DNA gel electrophoresis to assess the role of UVB-induced anergy and/or cell death. To extend our studies to the clinical setting and to promote chimerism and tolerance to organ allografts, we have further studied the effects of UVB irradiation combined with the commonly used immunosuppressive agents (cyclosporine, azathioprine, and methylprednisolone) on human T cells in proliferative in vitro assays. When cytotoxic and proliferative responses to allogeneic cells or to PHA stimulation were evaluated in LDA, the use of increasing doses of UVB irradiation resulted in a dose-dependent decrease in proliferative and cytotoxic responses of T-cells as seen by decreases in precursor frequencies. The results of proliferative T-cell assays suggest an additive immunosuppressive effect of various immunosuppressive drugs when combined with UVB irradiation. Gel electrophoresis of DNA derived from resting and activated, UVB-irradiated PBLs showed apoptosis at all UVB doses used. FACS analysis of UVB-treated CD2+ cells resulted in a UVB dose-related decrease in cell numbers that correlated with viability studies. It appears that UVB irradiation of both activated and resting PBLs induces programmed cell death but not anergy of T-cells.
Yaron
I
I
Department of Surgery, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Yaron
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R
Oluwole
S F
SF
Hardy
M A
MA
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D001379:Azathioprine / Q000494:pharmacology*; D017635:Clonal Anergy / Q000187:drug effects / Q000528:radiation effects; D016572:Cyclosporine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D008775:Methylprednisolone / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D008775:Methylprednisolone