Interactions between CD40 and CD40 ligand (CD40L) play a major role in direct CD4+ T cell–B cell collaboration, but the influence on CD8+ T cells — through the antigen-presenting cells (APCs) — has been assumed to be indirect. In September 20 Science, Christine Bourgeois and colleagues at INSERM U345, Institut Necker, Paris, France, show that, like B cells, CD8+ T cells receive CD4 help directly through CD40 and this interaction is fundamental for CD8+ T cell memory generation (Science, 297:2060-2063, September 20, 2002).

Bourgeois et al. used mice that had independent CD8+ T cells and CD4+ T cells, and genetically manipulated APCs. They observed that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by APCs. In addition, they showed that activated CD4+ and...

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