Lithium potentiates antigen-dependent stimulation of lymphocytes only under suboptimal conditions

Immunization of hamsters with DNP-BSA in either Freund's complete or incomplete adjuvant led to the induction of antigen reactive lymph node cells. As assessed by in vitro lymphocyte stimulation assays, antigen in complete adjuvant was more effective than antigen in incomplete adjuvant in inducing immunity. Supplementing antigen-stimulated cultures from animals 14 days post-immunization with LiCl led to no enhancement of tritiated thymidine incorporation into cells from animals immunized with antigen in complete adjuvant, but did enhance antigen-dependent stimulation of cells from animals immunized with antigen + incomplete adjuvant. LiCl was, however, able to enhance stimulation of cells from animals immunized with antigen + complete adjuvant at 22 and 29 days post-immunization, when in vitro responsiveness was declining. Lymph node cells from animals optimally immunized antigen + complete adjuvant were fractionated by passage over Sephadex G-10 columns. Sephadex G-10 non-adherent cells, deficient in cells such as macrophages, exhibited a depressed responsiveness to antigen, compared to unfractionated cells, and responsiveness was not restored by LiCl. Stimulation of cells by antigen was found to be inhibited by supplementing the cultures with theophylline or dibutyryl cyclic AMP and this inhibition could be reversed by LiCl. Lithium would, therefore, appear to be able to influence lymphocyte adenylate cyclase. Thus, LiCl can exert an immunopharmacologic effect on in vitro antigen stimulation primarily when conditions are suboptimal, possibly through an influence on cyclic AMP metabolism.