Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.
The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting 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 cells indicating that the GD3 molecule is not a marker for a certain functional T cell subset. In contrast to anti-CD3 mediated activation, the responsiveness of T cells to stimulation via GD3 was dependent on the cell surface expression of the molecule and could be enhanced by costimulation via CD2, CD3, CD26 or CD28. In addition, anti-GD3 antibodies delivered a potent costimulatory signal for antigen-induced proliferation of CD4+ T lymphocytes. In summary, our experiments illuminate the mechanisms of anti-GD3 antibody induced T cell activation.
Schlaak
J F
JF
First Department of Medicine, University of Mainz, Germany.
Claus
C
C
Meyer zum Büschenfelde
K H
KH
Dippold
W
W
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000032:analysis / Q000502:physiology; D015704:CD4 Antigens / Q000502:physiology; D018968:CD58 Antigens; D016572:Cyclosporine / Q000494:pharmacology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D018968:CD58 Antigens; D005732:Gangliosides; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C026226:ganglioside, GD3; D016572:Cyclosporine