title: Agonistic anti-CD40 enhances the CD8+ T cell response during vesicular stomatitis virus infection.
abstract: Intracellular pathogens are capable of inducing vigorous CD8+ T cell responses. However, we do not entirely understand the factors driving the generation of large pools of highly protective memory CD8+ T cells. Here, we studied the generation of endogenous ovalbumin-specific memory CD8+ T cells following infection with recombinant vesicular stomatitis virus (VSV) and Listeria monocytogenes (LM). VSV infection resulted in the generation of a large ovalbumin-specific memory CD8+ T cell population, which provided minimal protective immunity that waned with time. In contrast, the CD8+ T cell population of LM-ova provided protective immunity and remained stable with time. Agonistic CD40 stimulation during CD8+ T cell priming in response to VSV infection enabled the resultant memory CD8+ T cell population to provide strong protective immunity against secondary infection. Enhanced protective immunity by agonistic anti-CD40 was dependent on CD70. Agonistic anti-CD40 not only enhanced the size of the resultant memory CD8+ T cell population, but enhanced their polyfunctionality and sensitivity to antigen. Our data suggest that immunomodulation of CD40 signaling may be a key adjuvant to enhance CD8+ T cell response during development of VSV vaccine strategies.
authors.affiliation: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Julianne M
authors.initials: JM
authors.lastname: Zickovich
authors.affiliation: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Susan I
authors.initials: SI
authors.lastname: Meyer
authors.affiliation: Department of Immunology, Juntendo University, School of Medicine, Toyko, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Obar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D053282:CD27 Ligand / Q000276:immunology*; D019013:CD40 Antigens / Q000819:agonists* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D007167:Immunotherapy; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054243:Vesicular Stomatitis / Q000276:immunology / Q000628:therapy*; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D019013:CD40 Antigens