Help for cytotoxic-T-cell responses is mediated by CD4O signalling

Abstract

Cytotoxic T lymphocytes (CTLs) which carry the CDS antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effectors can act alone when killing target cells, their differentiation from naive CDS-positive T cells is often dependent on 'help' from CD4-positive helper T (TH) cells1"4. Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the TU cell and the CTL recognize antigen on the same antigen-presenting cell2'1. One explanation for this requirement is that TH cells are needed to convert the antigen-presenting cell into a cell that is fully competent to prime CTL5. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TM cells, indicating that T-cell 'help', at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell.