Modulation of cell-mediated immunity with 5-azapyrimidine nucleosides.

5-azacytidine [5-AzCR] and 5-aza-2'-deoxycytidine [5-AzCdR] can produce an immunosuppressive or an immunostimulatory effect on the graft-versus-host or host-versus-graft reactions in the regional popliteal lymph node of the mouse. The result depends on the dose of the drug and the time between its administration and induction of the cell-mediated immune response. Syngeneic spleen cells are capable of inducing regional lymphadenomegaly if injected into the footpads of recipients treated 1 day previously or concurrently with 5-AzCR or 5-AzCdR. Spleen cells from allogeneic and syngeneic donors treated with 5-AzCR or 5-AzCdR in vivo or in vitro can elicit greater regional lymphadenomegaly than the untreated cells. Both drugs not only seem to influence the proliferative activity of effector and regulatory populations of immunocompetent cells, but they probably also change their recognition ability and immunogenic properties.