D-penicillamine: mitogenic effect on mouse, rat and human spleen lymphocytes

The effect of D-penicillamine (D-Pen) on the proliferation of cultures of normal mouse, rat, and human spleen lymphocytes and peripheral blood lymphocytes was examined. D-Pen in concentrations of 2 x 10(-3) M to 8 x 10(-3) M in serum-free and in serum-containing medium resulted in a highly significant incorporation of 3H-TdR by normal mouse and rat spleen cells. Enhanced incorporation of 3H-TdR by normal human spleen cells only occurred in serum-containing medium. D-Pen in concentrations of 10(-4) M to 10(-3) M in serum-free and serum-containing medium resulted in significant inhibition of 3H-TdR incorporation by normal and mitogen-stimulated mouse and rat spleen cells. Doses of D-Pen greater than 2 x 10(-2) M strongly inhibited 3H-TdR incorporation by both normal and mitogen-stimulated mouse, rat, and human spleen cells and peripheral blood cells. The latter cells were not stimulated or inhibited at lower concentrations of D-Pen. Results from cell depletion and enriching procedures (specific antibody +C' cell killing, employment of athymic, nude spleen cells, adherent and phagocytic cell removal, E rosette cell separation procedures) suggested that target cells in the mouse spleen for D-Pen activation are non-adherent B cells whereas the D-Pen responsive cells in the human spleen probably are T cells.