title: Specific suppression of lupus-like graft-versus-host disease using extracorporeal photochemical attenuation of effector lymphocytes.
abstract: (C57BL/6 x DBA/2)F1 (B6D2F1) mice inoculated with parental DBA/2 (D2) splenocytes develop chronic stimulatory graft-versus-host reaction with many of the clinical manifestations of systemic lupus erythematosus. This investigation tested the ability of 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light-treated D2 cells, primed to contain an expanded population of T cells specific for B6D2F1 major histocompatability complex antigens, to treat and/or prevent such systemic lupus erythematosus-like disease. 8-MOP/UVA-treated cells from B6D2F1-primed D2 donors were inoculated into B6D2F1 recipients weekly six to ten times, either before or after initiating graft-versus-host disease with normal D2 cells. A third group of B6D2F1 recipients were vaccinated weekly six times before disease initiation using 8-MOP/UVA-attenuated, B6D2F1-primed D2 cells that had been secondarily stimulated and expanded in vitro in the presence of irradiated B6D2F1 targets and interleukin-2. Control B6D2F1 mice were vaccinated with 8-MOP/UVA-treated D2 cells stimulated in vitro and/or in vivo with (C3H/HeJ x DBA/2)F1 cells. Only mice vaccinated with 8-MOP/UVA-attenuated D2-anti-B6D2F1 cells that were secondarily stimulated and expanded in vitro exhibited differences from controls when measured by the clinical parameters of ascites formation, and mean survival (p < 0.025). These groups also differed significantly in mean antinuclear antibody titer measured 14 weeks after disease initiation (p < 0.05). At 28 weeks, histologic evidence of systemic lupus erythematosus-like kidney disease was found only in the control group. These results indicate that photochemically attenuated D2-anti-B6D2F1 cells primed in vivo and secondarily stimulated and expanded in vitro are capable of vaccinating recipients against progression of graft-versus-host reaction-initiated systemic lupus erythematosus-like disease.
authors: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut.
authors: M
authors: M
authors: Girardi
authors: P
authors: P
authors: Herreid
authors: R E
authors: RE
authors: Tigelaar
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001201:Ascites / Q000209:etiology / Q000276:immunology; D001327:Autoimmune Diseases / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006087:Graft vs Host Reaction; D016219:Immunotherapy, Adoptive; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011701:PUVA Therapy; D013601:T-Lymphocytes; D014611:Vaccination
chemical_list: D000974:Antibodies, Antinuclear