Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms.

6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or azathioprine inhibitory effects on the MLR. These results show that azathioprine and 6-MP suppress the MLR by different mechanisms.