title: Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection.
abstract: CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacterial products can directly activate APC through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for the efficient priming of naive T cells. It remains unclear what role CD4 T cell help and various costimulation pathways play in the development of CD8 T cell responses during bacterial infection. In this study, we examined these questions using an intracellular bacterium, Listeria monocytogenes, as a model of infection. In CD4 T cell-depleted, CD4(-/-), and MHC class II(-/-) mice, L. monocytogenes infection induced CD8 T cell activation and primed epitope-specific CD8 T cells to levels commensurate with those in normal C57BL/6 mice. Furthermore, these epitope-specific CD8 T cells established long-term memory in CD4(-/-) mice that was capable of mounting a protective recall response. In vitro analysis showed that L. monocytogenes directly stimulated the activation and maturation of murine dendritic cells. The CD8 T cell response to L. monocytogenes was normal in CD40L(-/-) mice but defective in CD28(-/-) and CD137L(-/-) mice. These data show that in situations where infectious agents or immunogens can directly activate APC, CD8 T cell responses are less dependent on CD4 T cell help via the CD40-CD40L pathway but involve costimulation through CD137-CD137L and B7-CD28 interactions.
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: Joyce
authors.initials: J
authors.lastname: Tan
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
mesh_terms: D053330:4-1BB Ligand; D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology; D023201:CD40 Ligand / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008024:Ligands; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D008211:Lymphocyte Cooperation / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D015704:CD4 Antigens; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand