Administration of exogenous RA selectively intensifies GVHD of the colon. Lethally irradiated Balb/c mice received a transplant of 10 × 106 B6 BM alone (○) or together with B6 spleen cells (adjusted to yield a dose of 0.6 × 106 T cells). Cohorts of mice that received adjunctive spleen cells were then treated by intraperitoneal injection with either DMSO (▪) or RA (●)(450 μg/mouse) every other day beginning on the day of transplantation until day 20. (A) Overall survival. Data are cumulative results of 3 experiments (n = 6 for BM control group, n = 12 for both DMSO- and RA-treated groups). (B) Mean percent initial body weight of recipient mice transplanted as in panel A over the first 35 days. (C) Lethally irradiated Balb/c mice were transplanted with B6 BM and spleen cells as above with the exception that the spleen cell dose was adjusted to yield a dose of 0.3 × 106 T cells. Groups were then treated with either DMSO or RA. Mice were killed 5 weeks after transplantation. Pathological damage in the tongue, liver, lung, and colon was examined using a semiquantitative scoring system as described in the Material and Methods section. Data are presented as the mean (± standard error of the mean) and are the cumulative results from 3 experiments (n = 12 for both groups). Statistics: **P ≤ .01. (D) Histology of tongue, liver, lung, and colon from representative Balb/c recipients transplanted with B6 BM and spleen cells and treated with either DMSO or RA. Tongues in DMSO- and RA-treated mice reveal lymphocytic infiltration into the epidermis. Livers in the 2 groups show mononuclear cell infiltration in the portal triads, while lungs demonstrate both perivascular cuffing attributable to mononuclear cells and associated interstitial inflammation. Colon in DMSO-treated animals demonstrates loss of mucin and lamina propria inflammation but preservation of crypt cell architecture. Conversely, RA-treated mice show extensive loss of crypts with goblet cell depletion and inflammation extending into the muscle. Original magnification is 200× for liver, colon, and tongue images and 100× for lung images.
