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  • Title: CD40 ligand induction on T cell subsets by peptide-presenting B cells: implications for development of the primary T and B cell response.
    Author: Jaiswal AI, Croft M.
    Journal: J Immunol; 1997 Sep 01; 159(5):2282-91. PubMed ID: 9278317.
    Abstract:
    Recent data suggest that CD40 ligand (CD40L)-CD40 interactions are essential for up-regulation of costimulatory activity on APC and that efficient induction of CD40L may be pivotal to the success of a CD4 T cell response. CD40L is regulated primarily by TCR signaling, but high level expression on a naive T cell appears to require additional interactions between T cell coreceptors and APC accessory molecules. The data reported here show that resting B cells presenting peptide Ag, in contrast to both dendritic cells and preactivated B cells, induce very little CD40L on naive CD4 cells, which in turn is insufficient to promote APC costimulatory activity. We also show, however, that previously activated effector T cells have enhanced responsiveness to Ag when accessory molecule help is limiting and consequently can express high levels of CD40L after interaction with resting B cells. High level CD40L expression correlated with B cell activation and up-regulation of costimulatory activity; however, blocking studies showed that CD40L was only partially responsible for these phenomena. These studies reinforce the notion that resting B cells may be tolerogenic for naive CD4 cells in part because of inefficient CD40L induction. The data also suggest that a successful primary T cell response will only occur if either the initial interaction is with a dendritic cell followed by subsequent interactions of the effector T cells with resting APC or if nonspecific inflammatory stimuli up-regulate accessory molecule expression on resting APC before an encounter with the naive T cell.
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