title: Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response.
abstract: CD4 T lymphocytes regulate the adaptive immune response to most viruses, both by providing help to CD8 T cells and B cells as well as through direct antiviral activity. Currently, no mouse cytomegalovirus (MCMV)-specific CD4 T cell responses are known. In this study, we identify and characterize 15 I-A(b)-restricted CD4 T cell responses specific for MCMV epitopes. CD4 T cells accumulate to high levels in the spleen and lungs during acute infection and produce multiple cytokines (IFN-gamma, TNF, IL-2, IL-10, and IL-17). Interestingly, IL-17 and IFN-gamma production within epitope-specific cells was found to be mutually exclusive. CD4 T cells recognizing a peptide derived from m09 were only detectable at later times of infection and displayed a unique cytokine production profile. In total, this study reveals that the MCMV-specific CD4 T cell response is complex and functionally diverse, highlighting its important role in controlling this persistent pathogen.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse