ANTIGEN PRESENTING CELL-DERIVED COSTIMULATORY SIGNALS CAN SELECTIVELY REGULATE IL-2 AND IL-4 PRODUCTION FROM A T(H)O CELL HYBRIDOMA

T(h)0 cells are a subpopulation of T(h) cells that produce both IL-2 and IL-4. In order to study the selective regulation of lymphokines in T(h)0 cells, a T(h)0 cell hybridoma, GA15, was generated by fusing a T(h)2 clone with the thymoma BW5147. The pattern of lymphokines secreted by GA15 was found to depend on the antigen presenting cells (APC) used for stimulation. When GA15 was stimulated with antigen and splenocytes, both IL-2 and IL-4 were produced. However, when the B cell hybridoma LB was used as APC, only IL-2 was detected. Although LB cells could not stimulate IL-4 production, they were more potent than were spleen cells at inducing IL-2 production, demonstrating that the difference between the two APC populations was qualitative rather than quantitative. Similar results were seen upon stimulation with concanavalin A or anti-CD3epsilon mAb. Regulation of interferon-gamma production paralleled regulation of IL-4 production. The failure of LB cells to stimulate IL-4 production was not due to inhibition or consumption of IL-4 and the activity could not be restored by adding IL-1, spleen cell supernatants or spleen cells lacking the appropriate MHC molecule. Finally, the parent T(h)2 clone used in the fusion showed a similar inability to produce IL-4 in response to LB cells. These data indicate that APC-derived co-stimulatory signals can selectively affect IL-2 and IL-4 production in a T(h)0 cell hybridoma. Therefore, the choice of APC may lead to selective stimulation of particular lymphokines by acting on T(h)0 cells.