Stimulation of T lymphocyte proliferation by monoclonal antibodies against G(D3) ganglioside

Cell-surface gangliosides are presumed to play a role in cell growth and differentiation. With the use of monoclonal antibodies directed against G(D3), a disialoganglioside expressed predominantly by cells of neuroectodermal origin, we have found that G(D3) is expressed by a subpopulation of cells of the immune system including: 1) fetal thymocytes in subcortical regions and near vessels, 2) lymph node lymphocytes in interfollicular areas and near vessels, and 3) a small subset of T cells in the peripheral blood. Mouse monoclonal antibodies (two IgGs, one IgM, and F(ab')₂ fragments) reacting with G(D3) were found to stimulate proliferation of T cells derived from peripheral blood. Proliferation of T cells was observed even in cultures depleted of macrophages, suggesting that activation by anti-G(D3) was not dependent on the presence of accessory cells. T cell proliferation was maximum between days 5 and 7 of stimulation and was preceded by expression of interleukin 2 receptors. No stimulation was observed with control antibodies of the identical isotype or with monoclonal antibodies recognizing the gangliosides G(D2) or G(M2). During stimulation by anti-G(D3) monoclonal antibodies, there was an expansion of the G(D3)⁺ pool of T cells, but depletion of G(D3)⁺ T cells prior to stimulation abrogated the response. Proliferation induced by binding to G(D3) could be augmented by exogenous interleukin 2 and phytohemagglutinin. Anti-CD3 (T3) monoclonal antibodies had little or no effect. These results demonstrate that binding to G(D3) on the surface of T cells can elicit signals for T cell proliferation.