Role of interleukins 1 and 2 on human thymocyte mitogen activation

The effects of d-penicillamine on proliferation and polyclonal activation of lymphocytes were studied in cultures of spleen cells from a variety of murine strains. Inclusion in serum-free or serum-containing medium of optimal concentrations of d-penicillamine resulted in the uptake of tritiated thymidine in a dose-dependent fashion, with both lower and higher doses causing less marked effects. The kinetic peak of these responses was found to occur at Day 2 of culture. Experiments examining the responsiveness of B-cell-enriched and T-cell-enriched populations demonstrated that d-penicillamine, like 2-mercaptoethanol, stimulates both types of cell. The magnitude of the response remained unchanged in populations depleted of adherent cells. In correlation with previous results seen for 2-ME, d-penicillamine was mitogenically active both in reduced and oxidized forms. The oxidized form failed to enhance the response to LPS, in contrast to the marked effect of the reduced form. Additionally, d-penicillamine failed to evoke a mitogenic response from B cells of CBA/N mice, a strain characterized by a deficit in the function of a particular set of mature B cells. Young mice from autoimmune strains responded to d-penicillamine as well as normal mice did. No relationship could be observed between responsiveness to d-penicillamine and the H-2 phenotype of the cell donor, and in A/J mice hyporesponsiveness was shown to be a function of their background rather than H-2. d-Penicillamine was found to function as a polyclonal B-cell activator, and to significantly enhance the primary humoral immune response to sheep erythrocytes in vitro. These immunomodulatory effects of d-penicillamine are discussed in relation to possible pathogenetic mechanisms of its spectrum of autoimmune side effects.