T-CELL HELP FOR CYTOTOXIC T-LYMPHOCYTES IS MEDIATED BY CD40-CD40L INTERACTIONS

Although in vivo priming of CD8(+) cytotoxic T lymphocytes (CTLs) gene rally requires the participation of CD4(+) T-helper lymphocytes(1,2), the nature of the 'help' provided to CTLs is unknown(3). One widely he ld view is that help for CTLs is mediated by cytokines produced by T-h elper cells activated in proximity to the CTL precursor at the surface of an antigen-presenting cell (APC)(4). An alternative theory is that , rather than being directly supplied to the CTL by the helper cell, h elp is delivered through activation of the APC, which can then prime t he CTL directly(5). CD40 and its ligand, CD40L, may activate the APC t o allow CTL priming. CD40L is expressed on the surface of activated CD 4(+) T-helper cells and is involved in their activation and in the dev elopment of their effector functions(6,7). Ligation of CD40 on the sur face of APCs such as dendritic cells, macrophages and B cells greatly increases their antigen-presentation and co-stimulatory capacity(8-11) . Here we report that signalling through CD40 can replace CD4(+) T-hel per cells in priming of helper-dependent CD8(+) CTL responses. Blockad e of CD40L inhibits CTL priming; this inhibition is overcome by signal ling through CD40. CD40-CD40L interactions are therefore vital in the delivery of T-cell help for CTL priming.