In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses.
Given the key role CD8+ T cells play in controlling viral infection, strategies to enhance these responses may have important clinical applications. We found that in vivo CD137 stimulation with an agonistic monoclonal antibody enhanced the primary CD8+ T cell response to influenza type A viral infection in mice. Stimulation of CD137 increased the absolute number of CD8+ T cells to influenza epitopes in the lungs of infected animals, preferentially expanded CD8+ T cells that recognized nondominant epitopes and greatly enhanced direct ex vivo cytotoxicity. CD137 stimulation also restored the CD8+ T cell response to the immunodominant influenza epitope in CD28-/- mice. Thus, in vivo CD137 stimulation enhances and broadens the CD8+ T cell response to influenza virus and can restore the CD8+ T cell response when CD28 costimulation is absent. This suggests that CD137 stimulation may be useful as a strategy to enhance the CD8+ T cell response to viruses.
Halstead
E Scott
ES
Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, PA, USA.
Mueller
Yvonne M
YM
Altman
John D
JD
Katsikis
Peter D
PD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000096:biosynthesis; D015703:Antigens, CD; D000956:Antigens, Viral; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D017475:Receptors, Nerve Growth Factor / Q000819:agonists / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000378:metabolism*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; D000956:Antigens, Viral; D018106:CD28 Antigens; D000939:Epitopes; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9