Prediction of graft prolongation by mixed lymphocyte culture following anti-CD4 monoclonal antibody treatment among different donor-recipient combinations

This study was conducted to examine whether mixed lymphocyte culture (MLC) could be used as a predictor of the efficacy of anti-CD4 monoclonal antibod y (MAb) immunosuppression in vivo in a mouse model, C57BL/10 or BALB/c hear ts were transplanted into C3H.He recipients. Anti-CD4 MAb administration pr olonged graft survival, but there was a clear difference between the two do nor-recipient combinations studied, the median survival time (MST) being >1 00 days in the C57BL/10 --> C3H group, and 17 days in the BALB/c --> C3H gr oup. Anti-CDS MAb prolonged the survival of C57BL/10 hearts slightly to a M ST of 22 days, but the BALB/c hearts were rejected at control rates. Combin ing anti-CD4 and anti-CDS antibody therapy prolonged the survival of C57BL/ 10 hearts indefinitely, but had little effect on the survival of BALB/c gra fts, achieving an MST of only 24 days. Next, MLCs were performed in the pre sence and absence of the MAbs and compared with the graft survival data. Th e inhibition rates in the MLC, being the C3H lymph node cell responder, cor related well with graft survival. When three kinds of C3H responder cells, namely lymph node (LN) cells, T cells, and CD4(+) cells, were examined to d etermine which was the most suitable for predicting graft survival, the MLC results showed that the responses of LN cells correlated most closely with graft outcome. In conclusion, MLC using LN cells as the responder is a use ful tool for predicting allograft survival induced by anti-CD4 MAb therapy.