Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells.
Murine primary antiviral cytotoxic T cell (CTL) responses are often induced in the absence of Th cells. In this study, we show that virus-like particles, if combined with DNA rich in CpG motifs, efficiently trigger primary CTL responses and comparable frequencies of memory CTLs in the presence or absence of T help. However, memory CTLs primed in the absence of T help failed to proliferate upon viral challenge. Nevertheless, they were efficiently recruited to sites of inflammation, indicating that T help may regulate the balance between proliferation-competent and migration-competent memory CTLs. Surprisingly, generation of proliferation-competent memory CTLs was completely independent of CD40 or CD40L, molecules commonly assumed to be central for mediating the beneficial effects of Th cells on CTL development. Thus, Th cells but not CD40/CD40L are key for the differentiation of proliferation-competent central memory CD8(+) T cells.
Bachmann
Martin F
MF
Cytos Biotechnology AG, Zurich-Schlieren, Switzerland. martin.bachmann@cytos.com
Schwarz
Katrin
K
Wolint
Petra
P
Meijerink
Edwin
E
Martin
Stephen
S
Manolova
Vania
V
Oxenius
Annette
A
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D018899:CpG Islands; D005260:Female; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D019013:CD40 Antigens; D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D023201:CD40 Ligand