Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
Cytotoxic T lymphocytes (CTLs) which carry the CD8 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 CD8-positive T cells is often dependent on 'help' from CD4-positive helper T (TH) cells. Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the TH cell and the CTL recognize antigen on the same antigen-presenting cell. 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 CTL. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH 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.
Bennett
S R
SR
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, PO The Royal Melbourne Hospital, Victoria, Australia.
Carbone
F R
FR
Karamalis
F
F
Flavell
R A
RA
Miller
J F
JF
Heath
W R
WR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D010047:Ovalbumin