title: ICAM-1-dependent tuning of memory CD8 T-cell responses following acute infection.
abstract: CD8 T-cell responses are critical for protection against intracellular pathogens and tumors. The induction and properties of these responses are governed by a series of integrated processes that rely heavily on cell-cell interactions. Intercellular adhesion molecule (ICAM)-1 functions to enhance the strength of antigenic stimulation, extend the duration of contact with antigen-presenting cells, and augment cytokine signals, which are all factors that influence peripheral CD8 T-cell differentiation. Although previous studies suggest that ICAM-1 is essential for establishing memory T-cell populations following peptide immunization, the roles of ICAM-1 in antiviral cellular immunity are less well understood. Here we show that, following a prototypic acute viral infection, the formation and maintenance of memory-phenotype CD127(hi), KLRG-1(lo) CD8 T cells does not require ICAM-1. Nevertheless, ICAM-1 expression on nonlymphocytes dictates the phenotypic and functional attributes of the antiviral CD8 T-cell populations that develop and promotes the gradual attrition of residual effector-like CD127(lo), KLRG-1(hi) CD8 T cells during the memory phase of the response. Although memory T cells do emerge and are maintained if ICAM-1 expression is abolished, the secondary proliferative capacity of these T cells is severely curtailed. Collectively, these studies reveal potential dual roles for ICAM-1 in both promoting the decay of effector responses and programming the sensitivity of memory CD8 T cells to secondary stimuli.
authors.affiliation: Departments of Microbiology and Genetics, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Cox
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D007156:Immunologic Memory / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: C090509:Icam1 protein, mouse; D053699:Interleukin-7 Receptor alpha Subunit; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1