title: Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection.
abstract: Efficient maintenance of memory CD8 T cells is central to long-term protective immunity. IL-7- and IL-15-driven homeostatic proliferation is essential for long-term memory CD8 T cell persistence after acute infections. During chronic infections, however, virus-specific CD8 T cells respond poorly to these cytokines. Yet, virus-specific CD8 T cells often persist for long periods of time during chronic infections. We have addressed this apparent paradox by examining the mechanism for maintaining virus-specific CD8 T cells during chronic infection. We find that homeostatic cytokines (e.g., IL-7/15), inflammatory signals, and priming of recent thymic emigrants are not sufficient to maintain virus-specific CD8 T cells over time during chronic infection. Rather, our results demonstrate that viral peptide is required for virus-specific CD8 T cell persistence during chronic infection. Moreover, this viral antigen-dependent maintenance results in a dramatically different type of T cell division than is normally observed during memory T cell homeostasis. Rather than undergoing slow, steady homeostatic turnover during chronic viral infection, CD8 T cells undergo extensive peptide-dependent division, yet cell numbers remain relatively stable. These results indicate that antigen-specific CD8 T cell responses during persisting infection are maintained by a mechanism distinct from that after acute infection.
authors.affiliation: Immunology Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Haina
authors.initials: H
authors.lastname: Shin
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Blackburn
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Blattman
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002455:Cell Division; D002908:Chronic Disease; D005260:Female; D019409:Interleukin-15 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D019409:Interleukin-15; D015851:Interleukin-7