CD28 molecule as a receptor-like function for accessory signals in cell-mediated augmentation of IL-2 production.

IL-2 production by PHA-stimulated MOLT 14 cells (a TcR gamma/delta-bearing human leukemic T cell line) and MOLT 16 cells (a TcR alpha/beta-bearing human leukemic T cell line) was markedly augmented by coculturing with BALL-1 cells ( a human leukemic B cell line), or with recombinant human interleukin-1 alpha (rhIL-1 alpha). We have previously shown that the augmentation of IL-2 production, induced by BALL-1 cells, requires cell to cell contact and is an IL-1-independent pathway. In this report, the expression of the CD28 molecule on MOLT 14 cells and MOLT 16 cells was examined for its role in IL-2 production augmented by BALL-1 cells. A 1-hr preincubation of MOLT 14 cells and MOLT 16 cells with anti-CD28 mAb resulted in the inhibition of BALL-1 cell-induced augmentation of IL-2 production (90 and 62% inhibition of control, respectively). The inhibition was observed in a dose-dependent manner of anti-CD28 mAb added and reached a plateau level at concentrations of 0.05 micrograms/ml of anti-CD28 mAb. This was sufficient to cover all the CD28 molecules expressed on the surface of both T cells as detected by flow cytometric analysis. Flow cytometric analysis also showed that the inhibition was not due to a modulation of CD28 molecules. In contrast, the treatment with anti-CD28 mAb did not inhibit IL-2 production which was augmented by rhIL-1 alpha costimulator. These results suggest that the CD28 molecule on the T cells is important for the interaction with BALL-1 cells which causes the augmentation of IL-2 production and further imply that the CD28 molecule is a receptor for an accessory signal provided by BALL-1 cells.