title: Costimulatory signals potently modulate the T cell inhibitory capacity of the therapeutic CD11a antibody Efalizumab.
abstract: The therapeutic CD11a antibody Efalizumab interferes with psoriasis pathogenesis by blocking T cell activation and migration. We have performed a detailed analysis on its effects during the activation of human T cells and found that the capability of Efalizumab to inhibit proliferation and cytokine production of T cells critically depends on the quality and quantity of costimulatory signals. Efalizumab potently inhibited the proliferation and cytokine production of human T cells costimulated via ICOS, OX40, CD27 or 4-1BB, but did not significantly inhibit T cells that received stimuli via CD2 or CD28. The capacity of CD2 and CD28 signals to interfere with the T cell inhibitory effects of Efalizumab was also observed upon stimulation of T cells with allogeneic DC. Furthermore, studies with T cells from psoriasis patients indicated that Efalizumab therapy induces inhibition of T cell responses that can be reverted by CD2 or CD28 signals.
authors.affiliation: Institute of Immunology, Center of Physiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner M
authors.initials: WM
authors.lastname: Kuschei
authors.forename: Judith
authors.initials: J
authors.lastname: Leitner
authors.forename: Otto
authors.initials: O
authors.lastname: Majdic
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Katharina
authors.initials: K
authors.lastname: Grabmeier-Pfistershammer
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
mesh_terms: D053330:4-1BB Ligand / Q000494:pharmacology; D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology; D040881:CD11a Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018968:CD58 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D060945:Inducible T-Cell Co-Stimulator Ligand; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D018122:B7-1 Antigen; D040881:CD11a Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; C498514:ICOSLG protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D060945:Inducible T-Cell Co-Stimulator Ligand; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma; C472181:efalizumab