title: Secondary CD8+ T-cell responses are controlled by systemic inflammation.
abstract: Repeated infections and experimental prime-boost regimens frequently result in the generation of secondary (2°) CD8(+) T-cell responses. In contrast to primary (1°) CD8(+) T cells, the parameters that influence the abundance and phenotype of 2° effector and memory CD8(+) T-cell populations are largely unknown. Here, we analyze the impact of different booster infections, Ag curtailment, and systemic inflammation on the quality and quantity of secondary CD8(+) T-cell responses. We show that similar to 1° CD8(+) T-cell responses, the phenotype of 2° effector and memory CD8(+) T-cell populations is critically dependent on the nature of the infectious pathogen and the inflammatory milieu early after infection. In addition, systemic inflammation increases the number of 2° effector and memory CD8(+) T cells after booster infections and immunizations. Therefore, our data reveal new means to boost the number of 2° effector and memory CD8(+) T cells in prime-boost regimens and show a surprisingly high degree of plasticity in 2° memory CD8(+) T-cell phenotype that is controlled by systemic inflammation.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wirth
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Martin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Starbeck-Miller
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D037181:Lectins, C-Type; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011971:Receptors, Immunologic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000667:Ampicillin