T-cell costimulatory molecules: optimal targets for the treatment of allergic airway disease with monoclonal antibodies.
Current treatment for chronic allergic airway disease with anti-inflammatory agents is effective but not specific, and is symptomatic rather than curative. The present review article outlines the involvement of T cells by dissecting the various steps in which naive CD4+ T cells differentiate to allergen-specific, activated T cells of the TH2 type, which play a pivotal role in the pathogenesis of chronic allergic airway disease. Aiming at a concept for a highly specific therapy of this disease, various T cell costimulatory molecules (CD28, CD27, HVAM, BTLA, ICOS, OX40, CD30, 4-1BB, SLAM, CTLA-4, and PD-1) and the non-costimulatory molecule CD40L, all of them expressed on activated TH2 effector T cells, are discussed as potential targets for an antibody-based therapy. Considering various criteria, including T-cell specific expression and expression characteristics on resting versus activated T cells, reasons are given why ICOS and OX40 can be regarded as optimal targets for such an immunotherapy. Furthermore, arguments are put forward that strongly favor an immunodepletion strategy as compared to an immunoblockade approach, when heading for a specific, long-lasting therapy of chronic allergic airway disease.
Kroczek
Richard
R
Molecular Immunology, Robert Koch-Institute, Berlin, Germany. kroczek@rki.de
Hamelmann
Eckard
E
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D017730:Ki-1 Antigen / Q000378:metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D016207:Cytokines; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D017730:Ki-1 Antigen; D008565:Membrane Proteins; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand