M. Girardi et al., SPECIFIC SUPPRESSION OF LUPUS-LIKE GRAFT-VERSUS-HOST DISEASE USING EXTRACORPOREAL PHOTOCHEMICAL ATTENUATION OF EFFECTOR LYMPHOCYTES, Journal of investigative dermatology, 104(2), 1995, pp. 177-182
(C57BL/6 x DBA/2)F-1 (B6D2F(1)) mice inoculated with parental DBA/2 (D
2) splenocytes develop chronic stimulatory graft-versus-host reaction
with many of the clinical manifestations of systemic lupus erythematos
us. 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 B6D2F(1) major histocompat
ability complex antigens, to treat and/or prevent such systemic lupus
erythematosus-like disease. 8-MOP/UVA-treated cells from B6D2F(1)-prim
ed D2 donors were inoculated into B6D2F(1) recipients weekly six to te
n times, either before or after initiating graft-versus-host disease w
ith normal D2 cells. A third group of B6D2F(1) recipients were vaccina
ted weekly six times before disease initiation using 8-MOP/UVA-attenua
ted, B6D2F(1)-primed D2 cells that had been secondarily stimulated and
expanded in vitro in the presence of irradiated B6D2F(1) targets and
interleukin-2. Control B6D2F(1) mice were vaccinated with 8-MOP/UVA-tr
eated D2 cells stimulated in vitro and/or in vivo with (C3H/HeJ x DBA/
2)F-1 cells. Only mice vaccinated with 8-MOP/UVA-attenuated D2-anti-B6
D2F(1) cells that were secondarily stimulated and expanded in vitro ex
hibited differences from controls when measured by the clinical parame
ters of ascites formation, and mean survival (p < 0.025). These groups
also differed significantly in mean antinuclear antibody titer measur
ed 14 weeks after disease initiation (p < 0.05). At 28 weeks, histolog
ic evidence of systemic lupus erythematosus-like kidney disease was fo
und only in the control group. These results indicate that photochemic
ally attenuated D2-anti-B6D2F(1) 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.