ANTI-GD-3 ANTIBODIES ARE POTENT ACTIVATORS OF HUMAN GAMMA DELTA AND ALPHA/BETA POSITIVE T-CELLS/

The ganglioside GD3 has a variety of biological functions. These inclu de stimulatory effects on proliferation, natural killer activity and c ytokine production by freshly isolated peripheral T cells. In this stu dy we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4(+) and CD 8(+) as well as gamma/delta TCR positive T cells can be stimulated res ulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule . Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 ce lls indicating that the GD3 molecule is not a marker for a certain fun ctional T cell subset. In contrast to anti-CD3 mediated activation, th e responsiveness of T cells to stimulation via GD3 was dependent on th e cell surface expression of the molecule and could be enhanced by cos timulation via CD2, CD3, CD26 or CD28. In addition, anti-GD3 antibodie s delivered a potent costimulatory signal for antigen-induced prolifer ation of CD4(+) T lymphocytes. In summary, our experiments illuminate the mechanisms of anti-GD3 antibody induced T cell activation.