Differential effect of azathioprine on theta-antigenicity of mouse lymphocytes.

The effect of a single injection of 300 mg/Kg azathioprine on the lymphoid cells of normal mice has been studied. The proportions of θ-positive cells in the thymus, lymph nodes and spleen were examined using a Trypan Blue exclusion cytotoxicity test. Two anti-θ sera of different titre were employed in an attempt to evaluate changes in θ-antigenicity of these cells following azathioprine treatment. In the thymus the drug was found to deplete a particular population of cortical thymocytes without affecting the hydrocortisone-resistant cells. The ability of azathioprine-resistant thymocytes to absorb out the cytotoxic capacity of both antisera was not better than that of hydrocortisone-resistant thymocytes. This result was taken to indicate that, following azathioprine, the residual cells had a decreased frequency of the θ antigen and were in this respect more like hydrocortisone-resistant cells. It is also postulated that the two antisera were of different avidity. A decrease in antigenicity was also seen in lymph node cell populations from azathioprine-treated animals. It is therefore suggested that azathioprine given in heavy doses might have at least two effects on lymphoid cells: (i) it depletes certain populations; and (ii) it decreases the θ-antigenicity of others.