LIGATION OF CD40 ON DENDRITIC CELLS TRIGGERS PRODUCTION OF HIGH-LEVELS OF INTERLEUKIN-12 AND ENHANCES T-CELL STIMULATORY CAPACITY - T-T HELP VIA APC ACTIVATION

We investigated the possibility that T helper cells might enhance tile stimulatory function of dendritic cells (DCs). We found tl-lat ligati on of CD40 by CD40L triggers the production of extremely high levels o f bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha o r LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN- gamma production by T cells. These findings reveal a new role for CD40 -CD40L interaction in regulating DC function and are relevant to desig n therapeutic strategies using cultured DCs.