title: PD-1 ligands, negative regulators for activation of naive, memory, and recently activated human CD4+ T cells.
abstract: We examined the role of the PD-1 pathway on the activation of naive, memory, and recently activated human CD4+ T cells to test whether they responded differently. PD-1 ligand blockade modestly enhanced the percentage of responding T cells and production of IFN-gamma in a primary response to myelin basic protein (MBP) in normal donors. PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP). Blockade of PD-L1 alone had more effect than PD-L2, consistent with its higher expression on ex vivo dendritic cells; furthermore, anti-PD-L1 plus anti-PD-L2 resulted in the greatest enhancement. Moreover, PD-L1-Ig inhibited anti-CD3 induced activation of naive, memory, and recently activated CD4+ T cells. Together, our data demonstrated PD-1 functioned as a negative regulatory pathway on naive T cells during a primary response, and more potently, on memory or recently activated T cells during a secondary response.
authors.affiliation: Laboratory of Molecular Immunology, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Guifang
authors.initials: G
authors.lastname: Cai
authors.forename: Arnon
authors.initials: A
authors.lastname: Karni
authors.forename: Enedina M L
authors.initials: EM
authors.lastname: Oliveira
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
mesh_terms: D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; D016207:Cytokines; D008024:Ligands; D004676:Myelin Basic Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D013745:Tetanus Toxoid