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

U937 cells provide a co-stimulatory signal for CD3-mediated T-cell activati on which is independent of the CD28/CD80/CD86 interaction. This study set o ut to identify which molecules contribute to this co-stimulatory activity. Monoclonal antibodies (mAb) to the known accessory molecules CD11a, CD18, C D54 and CD45, all inhibited T-cell proliferation. Although CD11a/18 mAb inh ibited U937/T-cell cluster formation as well as proliferation, CD45 enhance d the size of the clusters formed, suggesting that this was not the only me chanism of inhibition. The alternative co-stimulatory pathway provided by U 937 cells preferentially stimulated a response in the CD18(+) T-cell popula tion, and this reflected the reduced sensitivity of CD8(+) T cells to CD28- mediated activation. Monoclonal antibodies to three molecules, CD53, CD98 a nd CD147, also inhibited U937-dependent T-cell proliferation. The mAb to CD 98 and CD147 were inhibitory when prepulsed on to the U937 cells, suggestin g an effect mediated by these molecules on the antigen-presenting cell.