Heterogeneity among viral antigen-specific CD4+ T cells and their de novo recruitment during persistent polyomavirus infection.
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.
Lin
Eugene
E
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kemball
Christopher C
CC
Hadley
Annette
A
Wilson
Jarad J
JJ
Hofstetter
Amelia R
AR
Pack
Christopher D
CD
Lukacher
Aron E
AE
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
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; C062481:VP1 protein, polyomavirus