EFFECT OF ULTRAVIOLET-B LIGHT ON LYMPHOCYTE ACTIVITY AT DOSES AT WHICH NORMAL BONE-MARROW STEM-CELLS ARE PRESERVED

Ultraviolet B (UVB) light is known to be immunosuppressive, but, proba bly because of a small UVC component in the emission spectra of some o f the UVB lamps used, reports vary on effective dose levels. To preven t potentially lethal graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, alloreactive donor T-cell activity must be suppressed. In this study, a narrow wavelength UVB lamp (TL01, 312 nm peak emission) was used to determine what doses of UVB were require d to abolish rat lymphocyte proliferation while simultaneously preserv ing rat bone marrow progenitor cell and primitive hematopoietic stem c ell viability. Lymphocyte proliferation, as measured by H-3-Thymidine incorporation, in response to lectin stimulation was abolished below d etection at doses greater than 3,500 J/m(2). When T-cell clonogenicity was measured in a limiting dilution assay, a small fraction (0.6%) wa s maintained at doses up to 4,000 J/m(2). Cytotoxic T-lymphocyte (CTL) activity was reduced after treatment with 4,000 J/m(2), but a signifi cant level of cytotoxicity was still maintained. Natural killer cell c ytolytic activity was not affected by doses up to 4,000 J/m(2). At 4,0 00 J/m(2) there was a 10% survival of colony-forming units-granulocyte -macrophage; a 1% and 4% survival of day-8 and day-12 colony-forming u nits-spleen, respectively; and 11% survival of marrow repopulating abi lity cells. Up to 25% of late cobblestone area forming cells (4 to 5 w eeks), reflecting the more immature hematopoietic stem cells, were pre served in bone marrow treated with 4,000 J/m(2), indicating that early stem cells are less sensitive to UVB damage than are more committed p rogenitor cells. Thus, a potential therapeutic window was established at approximately 4,000 J/m(2) using this light source, whereby the pot entially GVHD-inducing T cells were suppressed, but a sufficient propo rtion of the cells responsible for engraftment was maintained. (C) 199 6 by The American Society of Hematology.