T-cell help exposed

Abstract

Cytotoxic T cells (CTLs) recognizing peptide antigens bound to major histocompatibility complex (MHC) class I molecules are involved in the lysis of antigen-bearing target cells. Differentiation from naive CD8+ T cells to CTLs (CTL priming) is thought to often be dependent on help from CD4+ T helper (Th) cells. The nature of the help is to activate dendritic cells (DCs), which are known to be potent antigen-presenting cells, but not to directly activate CTLs (Ridge et al.[ 1 Ridge J.P. et al. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature. 1998; 393: 474-478 Crossref PubMed Scopus (2025) Google Scholar ]). CD40 ligand expressed on the surface of activated Th cells stimulates DCs via CD40 signalling to increase antigen presentation and co-stimulatory capacity, resulting in CTL priming. This requirement for Th cells to prime CTLs can be replaced by anti-CD40 monoclonal antibody (mAb) (Ridge et al.[ 1 Ridge J.P. et al. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature. 1998; 393: 474-478 Crossref PubMed Scopus (2025) Google Scholar ]; Bennett et al.[ 2 Bennett S.R.M. et al. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature. 1998; 393: 478-480 Crossref PubMed Scopus (1769) Google Scholar ]; Schoenberger et al.[ 3 Schoenberger S.P. et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions. Nature. 1998; 393: 480-483 Crossref PubMed Scopus (2154) Google Scholar ]). In MHC class II-deficient mice, which possess no Th cells, anti-CD40 mAb is capable of helping the induction of CTL responses. Thus, anti-CD40 mAb provides an opportunity for vaccination under circumstances that were previously difficult, either because of a lack of available class II-restricted antigenic determinants (as may occur with some tumour antigens) or because of a deficiency in CD4+ Th cells (as occurs in AIDS patients), as shown in MHC class II-deficient mice.