OX40/OX40L regulation of GVHD lethality and Stat-4 or Stat-6 signaling.

The regulation of GVHD lethality by the OX40/OX40L pathway does not depend upon Stat-4 or Stat-6 signaling in donor T cells. B6.BR recipients (n = 8 per group) were lethally irradiated, reconstituted with BALB/c BM, and given either no supplemental splenocytes or splenocytes (25 × 10⁶) from BALB/c or BALB/c Stat-4^−/− (panel A) or BALB/c Stat-6^−/−(panel B) donors. Cohorts of mice that received splenocytes were given either irrelevant, anti-OX40, or anti-OX40L mAb, as indicated. Anti-OX40L mAb infusion significantly reduced GVHD lethality. Conversely, anti-OX40 mAb significantly increased GVHD lethality in recipients of Stat-4^−/− splenocytes.