HELP FOR CYTOTOXIC-T-CELL RESPONSES IS MEDIATED BY CD40 SIGNALING

Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize a ntigens that are presented on target cells by the class I major histoc ompatibility complex. CTLs are responsible for the killing of antigen- bearing target cells, such as virus-infected cells. Although CTL effec ters can act alone when killing target cells, their differentiation fr om naive CD8-positive T cells is often dependent on 'help' from CD4-po sitive helper T (T-H) cells(1-4).Furthermore, for effective CTL primin g, this help must be provided in a cognate manner, such that both the T-H cell and the CTL recognize antigen on the same antigen-presenting cell(2,4). One explanation for this requirement is that T-H cells are needed to convert the antigen-presenting cell into a cell that is full y competent to prime CTL5. Here we show that signalling through CD40 o n the antigen-presenting cells can replace the requirement for T-H cel ls, indicating that T-cell 'help', at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-p resenting cell.