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, probably because of a small UVC component in the emission spectra of some of the UVB lamps used, reports vary on effective dose levels. To prevent 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 required to abolish rat lymphocyte proliferation while simultaneously preserving rat bone marrow progenitor cell and primitive hematopoietic stem cell viability. Lymphocyte proliferation, as measured by 3H-Thymidine incorporation, in response to lectin stimulation was abolished below detection at doses greater than 3,500 J/m2. When T-cell clonogenicity was measured in a limiting dilution assay, a small fraction (0.6%) was maintained at doses up to 4,000 J/m2. Cytotoxic T-lymphocyte (CTL) activity was reduced after treatment with 4,000 J/m2, but a significant level of cytotoxicity was still maintained. Natural killer cell cytolytic activity was not affected by doses up to 4,000 J/m2. At 4,000 J+m2 there was a 10% survival of colony-forming units-granulocyte-macrophage; a 1% and 4% survival of day-8 and day-12 colony-forming units-spleen, respectively; and 11% survival of marrow repopulating ability cells. Up to 25% of late cobblestone area forming cells (4 to 5 weeks), reflecting the more immature hematopoietic stem cells, were preserved in bone marrow treated with 4,000 J/m2, indicating that early stem cells are less sensitive to UVB damage than are more committed progenitor cells. Thus, a potential therapeutic window was established at approximately 4,000 J/m2 using this light source, whereby the potentially GVHD-inducing T cells were suppressed, but a sufficient proportion of the cells responsible for engraftment was maintained.
Gowing
H
H
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
Lawler
M
M
Hagenbeek
A
A
McCann
S R
SR
Pamphilon
D H
DH
Hudson
J
J
van Weelden
H
H
Braakman
E
E
Martens
A C
AC
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000528:radiation effects*; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D051381:Rats; D011914:Rats, Inbred BN; D014466:Ultraviolet Rays