title: T-cell costimulatory blockade in organ transplantation.
abstract: Before it became possible to derive T-cell lines and clones, initial experimentation on the activation requirements of T lymphocytes was performed on transformed cell lines, such as Jurkat. These studies, although technically correct, proved misleading as most transformed T cells can be activated by stimulation of the clonotypic T-cell receptor (TCR) alone. In contrast, once it became possible to study nontransformed T cells, it quickly became clear that TCR stimulation by itself is insufficient for optimal activation of naïve T cells, but in fact, induces a state of anergy. It then became clear that functional activation of T cells requires not only recognition of major histocompatibility complex (MHC) and peptide by the TCR, but also requires ligation of costimulatory receptors expressed on the cell surface.
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Maltzman
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D018968:CD58 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen / Q000502:physiology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D053278:OX40 Ligand / Q000502:physiology; D011323:Primates; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000502:physiology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D018106:CD28 Antigens; D019013:CD40 Antigens; D018968:CD58 Antigens; D060908:CTLA-4 Antigen; D060889:Inducible T-Cell Co-Stimulator Protein; D053278:OX40 Ligand; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D023201:CD40 Ligand