OX40 receptor regulation of GVHD in heavily irradiated MHC class I plus class II–disparate recipients.

Targeting of the OX40 receptor regulates GVHD in heavily irradiated MHC class I plus class II–disparate recipients. (A) B10.BR recipients (n = 8 per group) were lethally irradiated and reconstituted with B6 BM alone or containing supplemental splenocytes (S) from B6 donors. The splenocyte number × 10⁶is shown. Recipients of splenocytes received either irrelevant or anti-OX40 mAb beginning on the day before splenocyte administration as described in “Materials and methods.” (B) B6 recipients (n = 10 per group) were lethally irradiated and reconstituted with B10.BR BM. On day 21 after BMT, recipients were given splenocytes (5 × 10⁶) (DLI), followed 1 week later by challenge with acute myelogenous leukemia (AML) cells. Beginning on the day prior to DLI, cohorts of mice were given irrelevant or anti-OX40 mAb. Autopsies to detect gross evidence of AML cells were performed on mice that had received AML cells. (C) Mice (n = 8 per group per experiment) received transplants as described in panel A, except that splenocytes (15 × 10⁶) were obtained from either OX40^+/+(▴) or OX40^−/− (▵) donors. Data from 2 replicate experiments with similar results are pooled. In each instance, targeting of the OX40 receptor had a significant impact on survival rates.