Effect of blockade of the OX40/OX40L pathway on GVHD lethality in settings in which CD28 signaling is precluded.

Blockade of the OX40/OX40L pathway is effective in inhibiting GVHD lethality in settings in which CD28 signaling is precluded. (A-B) B10.BR recipients (n = 8 per group) were lethally irradiated and reconstituted with B6 BM, and cohorts were given C28^−/−splenocytes at 15 × 10⁶ (panel A) or 25 × 10⁶ (panel B). Recipients given splenocytes also received either irrelevant, anti-OX40, or anti-OX40L mAb. Survival was significantly different in groups receiving irrelevant mAb versus groups receiving either anti-OX40 or anti-OX40L mAb. (C) BALB/c OX40L^−/− mice or OX40L^+/+littermate controls (n = 5 per group) were lethally irradiated, reconstituted with B6 WT BM, and given either no T cells or B6 CD28^−/− T cells (3 × 10⁶). OX40L^−/− recipients had a significantly higher survival rate than OX40L^+/+ recipients.