title: Programmed death 1 regulates memory phenotype CD4 T cell accumulation, inhibits expansion of the effector memory phenotype subset and modulates production of effector cytokines.
abstract: Memory phenotype CD4 T cells are found in normal mice and arise through response to environmental antigens or homeostatic mechanisms. The factors that regulate the homeostasis of memory phenotype CD4 cells are not clear. In the present study we demonstrate that there is a marked accumulation of memory phenotype CD4 cells, specifically of the effector memory (T(EM)) phenotype, in lymphoid organs and tissues of mice deficient for the negative co-stimulatory receptor programmed death 1 (PD-1). This can be correlated with decreased apoptosis but not with enhanced homeostatic turnover potential of these cells. PD-1 ablation increased the frequency of memory phenotype CD4 IFN-γ producers but decreased the respective frequency of IL-17A-producing cells. In particular, IFN-γ producers were more abundant but IL-17A producing cells were more scarce among PD-1 KO T(EM)-phenotype cells relative to WT. Transfer of peripheral naïve CD4 T cells suggested that accumulated PD-1 KO T(EM)-phenotype cells are of peripheral and not of thymic origin. This accumulation effect was mediated by CD4 cell-intrinsic mechanisms as shown by mixed bone marrow chimera experiments. Naïve PD-1 KO CD4 T cells gave rise to higher numbers of TEM-phenotype lymphopenia-induced proliferation memory cells. In conclusion, we provide evidence that PD-1 has an important role in determining the composition and functional aspects of memory phenotype CD4 T cell pool.
authors: Institute of Molecular Biology and Biotechnology FORTH- Hellas, GR-70013 Heraklio, Crete, Greece.
authors: Joanna J
authors: JJ
authors: Charlton
authors: Institute of Molecular Biology and Biotechnology FORTH- Hellas, GR-70013 Heraklio, Crete, Greece.
authors: Debbie
authors: D
authors: Tsoukatou
authors: Institute of Molecular Biology and Biotechnology FORTH- Hellas, GR-70013 Heraklio, Crete, Greece.
authors: Clio
authors: C
authors: Mamalaki
authors: Institute of Molecular Biology and Biotechnology FORTH- Hellas, GR-70013 Heraklio, Crete, Greece.
authors: Ioannis
authors: I
authors: Chatzidakis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D020382:Interleukin-18; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor