Augmentation of lymphocyte responses by monoclonal antibodies to the gangliosides GD3 and GD2: the role of protein kinase C, cyclic nucleotides, and intracellular calcium.
Previous studies have shown that MAb's against the gangliosides GD3 and GD2 may augment T cell responses to a variety of stimuli. We present evidence that antiganglioside MAb's, like PHA, increase intracellular cGMP and protein kinase C yet have no effect on intracellular Ca2+. Stimulation of T cells with MAb's to GD3 was associated with increased cGMP levels, particularly in the CD8+ T cell subset which showed the highest degree of potentiation by the MAb's. Augmentation of T cell responses by the MAb's to GD3 and GD2 was also mimicked by activation of PKC with phorbol esters but both agents together produced marked synergistic effects on cell division, suggesting they had different but complementary modes of action. Furthermore, use of neomycin to inhibit PKC activation only partially reversed the augmentation of proliferative responses by the antiganglioside MAb's. It did however inhibit the MAb-induced increase in IL2 production and IL2 receptor (Tac) expression. These studies suggest therefore that the potentiation of IL2 production by the MAb's against GD2 and GD3 was due to enhanced activation of PKC whereas their augmentation of proliferative responses appeared to be due to effects on late events in T cell activation and was associated with both increased cGMP levels and activation of PKC.
Hersey
P
P
Immunology and Oncology Unit, Mater Misericordiae Hospital at the Royal Newcastle Hospital, New South Wales, Australia.
Schibeci
S
S
Cheresh
D
D
D000911:Antibodies, Monoclonal / Q000276:immunology*; D002118:Calcium / Q000502:physiology*; D004789:Enzyme Activation; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009712:Nucleotides, Cyclic / Q000032:analysis / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; D009712:Nucleotides, Cyclic; D010835:Phytohemagglutinins; C026226:ganglioside, GD3; C019403:ganglioside, GD2; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium