Modulation of lymphocyte proliferation and immunoglobulin production by transferrin-gallium.

Gallium resembles iron with respect to transferrin (Tf) binding and cellular uptake via Tf receptors. We have previously shown that transferrin-gallium (Tf-Ga) complexes interfere with the cellular incorporation of iron and inhibit the proliferation of HL60 cells. Since mitogen-stimulated peripheral blood lymphocytes express Tf receptors, we examined the effect of Tf-Ga on lymphocyte proliferation and on immunoglobulin synthesis by B-lymphocytes. Tf-Ga inhibited phytohemagglutinin, pokeweed mitogen, and tetanus toxoid-stimulated lymphocyte proliferation by greater than 50%, an effect which appeared to be cytostatic rather than cytotoxic. In cocultures of T-lymphocytes or CD4+ T-lymphocytes and B-lymphocytes, Tf-Ga also inhibited pokeweed mitogen-stimulated immunoglobulin production by 84 to 100%. Tf-Ga inhibited both T-independent Epstein Barr virus-stimulated B-lymphocyte proliferation and immunoglobulin production; however, these effects appeared to be independent of each other, since immunoglobulin production was inhibited by 75% by a concentration of Tf-Ga which did not uniformly inhibit proliferation. Tf-Ga is capable of targeting Tf receptor-bearing T- and B-lymphocytes and interfering with their proliferation and function. Such effects may be of relevance to patients being treated with this metal. The potential immunosuppressive activity of gallium warrants further investigation.