title: Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro.
abstract: The characteristics of CD8+ T cells responsible for memory responses are still largely unknown. Particularly, it has not been determined whether different activation thresholds distinguish naive from memory CD8+ T cell populations. In most experimental systems, heterogeneous populations of primed CD8+ T cells can be identified in vivo after immunization. These cells differ in terms of cell cycle status, surface phenotype, and/or effector function. This heterogeneity has made it difficult to assess the activation threshold and the relative role of these subpopulations in memory responses. In this study we have used F5 T cell receptor transgenic mice to generate a homogeneous population of primed CD8+ T cells. In the F5 transgenic mice, peptide injection in vivo leads to activation of most peripheral CD8+ T cells. In vivo BrdU labeling has been used to follow primed T cells over time periods spanning several weeks after peptide immunization. Our results show that the majority of primed CD8+ T cells generated in this system are not cycling and express increased levels of CD44 and Ly6C. These cells remain responsive to secondary peptide challenge in vivo as evidenced by short term upregulation of activation markers such as CD69 and CD44. The activation thresholds of naive and primed CD8+ T cells were compared in vitro. We found that CD8+ T cells from primed mice are activated by peptide concentrations 10-50-fold lower than naive mice. In addition, the kinetics of interleukin 2R alpha chain upregulation by primed CD8+ T cells differ from naive CD8+ T cells. These primed hyperresponsive CD8+ T cells might play an important role in the memory response.
authors.affiliation: Laboratoire de Biologie Moleculaire et Cellulaire de Ecole Normale Superieure Lyon centre National de la Recherche Scientifique Unité Mixte de Recherche, France.
authors.forename: M
authors.initials: M
authors.lastname: Pihlgren
authors.forename: P M
authors.initials: PM
authors.lastname: Dubois
authors.forename: M
authors.initials: M
authors.lastname: Tomkowiak
authors.forename: T
authors.initials: T
authors.lastname: Sjögren
authors.forename: J
authors.initials: J
authors.lastname: Marvel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013934:Thymectomy; D015854:Up-Regulation; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D010446:Peptide Fragments; D000099192:CD69 Antigens