Photoinactivation of T-cell function with psoralen and UVA radiation suppresses the induction of experimental murine graft-versus-host disease across major histocompatibility barriers.
Bone marrow transplantation is employed in the treatment of a number of hematologic and malignant diseases. A major complication is the induction of graft-versus-host disease. Whereas removal of T lymphocytes from the donor marrow effectively reduces the incidence of graft-versus-host disease, the incidence of graft failure often increases when T cells are depleted from the transplanted marrow. In the current study, photoinactivation of the donor cells with 8-methoxypsoralen coupled with exposure to long-wavelength ultraviolet radiation (PUVA therapy) was used to inactivate the response of the donor T cells against the host. PUVA therapy suppressed the ability of spleen cells to respond to alloantigen in the in vitro mixed lymphocyte reaction. The induction of acute graft-versus-host disease across complete major histocompatibility barriers in lethally X-irradiated mice was significantly suppressed after bone marrow transplantation with photoinactivated bone marrow cells. Long-term survivors demonstrated allogeneic reconstitution and partial restoration of T-cell function. Because PUVA therapy had no inhibitory effect on hematopoiesis, these data suggest that using phototherapy to inactivate the alloreactivity of T cells may provide an alternative to purging T cells from the donor marrow, thus suppressing both the incidence of graft-versus-host disease and the incidence of graft failure.
Ullrich
S E
SE
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011701:PUVA Therapy; D013154:Spleen / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D003115:Colony-Stimulating Factors