CD40 ligation in vivo induces bystander proliferation of memory phenotype CD8 T cells.
Injection of agonistic anti-CD40 Abs into mice has been shown to amplify weak CD8 T cell responses to poorly immunogenic compounds and to convert T cell tolerance to T cell priming. In this study we demonstrate that anti-CD40 treatment of C57BL/6 mice, without Ag delivery, led to a marked increase in the number of memory phenotype CD4 and CD8 T cells. Adoptive transfer experiments using CD40-deficient hosts further revealed that the proliferative response of memory T cells, induced by systemic CD40 signaling, was dependent on CD40 expression of host APCs. CD40 ligation in vivo induced vigorous cell division of both memory phenotype and bona fide virus-specific memory CD8 T cells in a partially IL-15-dependent manner. However, only memory phenotype, but not Ag-experienced memory CD8 T cells increased in cell number after anti-CD40 treatment in vivo. Taken together our data show that activation of APC via CD40 induces a marked bystander proliferation of memory phenotype T cells. In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 T cells.
Koschella
Marie
M
Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany.
Voehringer
David
D
Pircher
Hanspeter
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D024201:Bystander Effect / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D016207:Cytokines; D018960:Hyaluronan Receptors; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D011070:Poly I-C