Effects of azathioprine on the human mixed lymphocyte reaction (MLR).

1 Azathioprine (36 .M) caused nearly complete and consistent inhibition of the mixed lymphocyte reaction (MLR).2 The inhibitory effect of azathioprine (36 gM) on the MLR decreased with increasing delay of drug addition.3 At 36 tM azathioprine was more inhibitory (34%) than 6-mercaptopurine.4 The addition of red blood cells or glutathione decreased but did not abolish the difference in activity between azathioprine and 6-MP on the MLR. 5 The inhibitory effect of azathioprine or 6-MP on the human MLR was partially reversed after 24 h by washing.6 Dithiothreitol (DTT) did not modify the reversibility of azathioprine inhibition by washing.7 Restimulation of the washed azathioprine treated MLR cultures after 24 h by the same or different allogeneic stimulating lymphocytes had no effect.8 The responding and stimulating lymphocytes were affected to the same extent by azathioprine.9 These results suggest that azathioprine does not inhibit the MLR by deleting antigen stimulated lymphocytes.They would be more in keeping with an action on the lymphocyte membrane.