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

Abstract

This study was conducted to examine whether mixed lymphocyte culture (MLC) could be used as a predictor of the efficacy of anti-CD4 monoclonal antibody (MAb) immunosuppression in vivo in a mouse model. C57BL/10 or BALB/c hearts were transplanted into C3H.He recipients. Anti-CD4 MAb administration prolonged graft survival, but there was a clear difference between the two donor-recipient combinations studied, the median survival time (MST) being >100 days in the C57BL/10 --> C3H group, and 17 days in the BALB/c --> C3H group. Anti-CD8 MAb prolonged the survival of C57BL/10 hearts slightly to a MST of 22 days, but the BALB/c hearts were rejected at control rates. Combining anti-CD4 and anti-CD8 antibody therapy prolonged the survival of C57BL/10 hearts indefinitely, but had little effect on the survival of BALB/c grafts, achieving an MST of only 24 days. Next, MLCs were performed in the presence and absence of the MAbs and compared with the graft survival data. The inhibition rates in the MLC, being the C3H lymph node cell responder, correlated well with graft survival. When three kinds of C3H responder cells, namely lymph node (LN) cells, T cells, and CD4+ cells, were examined to determine 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 useful tool for predicting allograft survival induced by anti-CD4 MAb therapy.