REQUIREMENT FOR CD40 LIGAND IN COSTIMULATION INDUCTION, T-CELL ACTIVATION, AND EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD 4(+) T cells was examined by investigation of the development of exper imental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein . These mice failed to develop EAE after priming with antigen, and CD4 (+) T cells remained quiescent and produced no inteferon-gamma (IFN-ga mma). T cells were primed to make IFN-gamma and induce EAE by providin g these mice with B7.1(+) antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo acti vation of CD4(+) T cells to produce IFN-gamma and to evoke autoimmunit y.