The effect of in vivo and in vitro methotrexate on lymphocyte proliferation as measured by the uptake of tritiated thymidine and tritiated guanosine.

In several studies methotrexate therapy of patients with rheumatoid arthritis has not been found to depress the lymphocyte response to mitogens measured by the uptake of tritiated thymidine. We have postulated two effects of methotrexate on stimulated lymphocytes in vitro: a decrease in cell proliferation, but also a relative increase in thymidine uptake reflecting a specific decrease in the intracellular thymidine pool. The increased incorporation of tritiated guanosine by mitogen-stimulated lymphocytes was found to be markedly depressed by methotrexate (1 x 10(-7) M) in vitro whereas the incorporation of thymidine was often unchanged. Thymidine uptake of lymphocytes may not be an appropriate measure of stimulation in the presence of methotrexate.