Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection.
Numerous microbes establish persistent infections, accompanied by antigen-specific CD8 T cell activation. Pathogen-specific T cells in chronically infected hosts are often phenotypically and functionally variable, as well as distinct from T cells responding to nonpersistent infections; this phenotypic heterogeneity has been attributed to an ongoing reencounter with antigen. Paradoxically, maintenance of memory CD8 T cells to acutely resolved infections is antigen independent, whereas there is a dependence on antigen for T cell survival in chronically infected hosts. Using two chronic viral infections, we demonstrate that new naive antigen-specific CD8 T cells are primed after the acute phase of infection. These newly recruited T cells are phenotypically distinct from those primed earlier. Long-lived antiviral CD8 T cells are defective in self-renewal, and lack of thymic output results in the decline of virus-specific CD8 T cells, indicating that newly generated T cells preserve antiviral CD8 T cell populations during chronic infection. These findings reveal a novel role for antigen in maintaining virus-specific CD8 T cells during persistent infection and provide insight toward understanding T cell differentiation in chronic infection.
Vezys
Vaiva
V
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Masopust
David
D
Kemball
Christopher C
CC
Barber
Daniel L
DL
O'Mara
Leigh A
LA
Larsen
Christian P
CP
Pearson
Thomas C
TC
Ahmed
Rafi
R
Lukacher
Aron E
AE
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011120:Polyomavirus / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
D000956:Antigens, Viral