Malignant plasma cell lines express a functional CD28 molecule

The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells

Malignant plasma cell lines express a functional CD28 molecule

The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells

Molecular characterization of U937-dependent T-cell co-stimulation

U937 cells provide a co-stimulatory signal for CD3-mediated T-cell activation which is independent of the CD28/CD80/CD86 interaction. This study set out to identify which molecules contribute to this co-stimulatory activity. Monoclonal antibodies (mAb) to the known accessory molecules CD11a, CD18, CD54 and CD45, all inhibited T-cell proliferation. Although CD11a/18 mAb inhibited U937/T-cell cluster formation as well as proliferation, CD45 enhanced the size of the clusters formed, suggesting that this was not the only mechanism of inhibition. The alternative co-stimulatory pathway provided by U937 cells preferentially stimulated a response in the CD18+ T-cell population, and this reflected the reduced sensitivity of CD8+ T cells to CD28-mediated activation. Monoclonal antibodies to three molecules, CD53, CD98 and CD147, also inhibited U937-dependent T-cell proliferation. The mAb to CD98 and CD147 were inhibitory when prepulsed on to the U937 cells, suggesting an effect mediated by these molecules on the antigen-presenting cell