title: Heterogeneity among viral antigen-specific CD4+ T cells and their de novo recruitment during persistent polyomavirus infection.
abstract: Virus-specific CD4(+) T cells optimize antiviral responses by providing help for antiviral humoral responses and CD8(+) T cell differentiation. Although CD4(+) T cell responses to viral infections that undergo complete clearance have been studied extensively, less is known about virus-specific CD4(+) T cell responses to viruses that persistently infect their hosts. Using a mouse polyomavirus (MPyV) infection model, we previously demonstrated that CD4(+) T cells are essential for recruiting naive MPyV-specific CD8(+) T cells in persistently infected mice. In this study, we defined two dominant MPyV-specific CD4(+) T cell populations, one directed toward an epitope derived from the nonstructural large T Ag and the other from the major viral capsid protein of MPyV. These MPyV-specific CD4(+) T cells vary in terms of their magnitude, functional profile, and phenotype during acute and persistent phases of infection. Using a minimally myeloablative-mixed bone marrow chimerism approach, we further show that naive virus-specific CD4(+) T cells, like anti-MPyV CD8(+) T cells, are primed de novo during persistent virus infection. In summary, these findings reveal quantitative and qualitative differences in the CD4(+) T cell response to a persistent virus infection and demonstrate that naive antiviral CD4(+) T cells are recruited during chronic polyomavirus infection.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Kemball
authors.forename: Annette
authors.initials: A
authors.lastname: Hadley
authors.forename: Jarad J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Hofstetter
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pack
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D036022:Capsid Proteins / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011120:Polyomavirus / Q000254:growth & development / Q000276:immunology; D027601:Polyomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; C062481:VP1 protein, polyomavirus