The role of ICOS and other costimulatory molecules in allergy and asthma.
Activation and differentiation of T cells play a critical role in the pathogenesis of allergies and asthma. Upon encounter with specific antigen, naïve T helper precursor (ThP) cells become activated, an event that is regulated not only by engagement of the T cell receptor (TCR) with peptide presented in the context of MHC class II molecules, but also by a number of costimulatory signals. CD28 engagement by B7-1 and B7-2 on resting ThP cells provides a critical signal for initial cell cycle progression, interleukin-2 production and clonal expansion. However, in recent years, other related members of the immunoglobulin (Ig) family, such as inducible costimulatory molecules (ICOS) and the TNF receptor family members which include OX40, have also been demonstrated to play an important role in providing unique and complementary signals that regulate the outcome of immune responses. These positive costimulatory signals are counterbalanced by signals that dampen down immune responses and include CTLA-4, PD-1 and the recently described Ig superfamily members BTLA and TIM-3. This review discusses the role of these costimulatory signals and their potential involvement in the pathogenesis of asthma and allergic responses.
Department of Mucosal Immunology and Pharmacology, Inflammation Division, Millennium Pharmaceuticals Inc., Cambridge, MA 02139, USA. Coyle@mpi.com
Anthony J
AJ
Coyle
Jose-Carlos
JC
Gutierrez-Ramos
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000276:immunology*; D018106:CD28 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D008565:Membrane Proteins / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000502:physiology; D011991:Receptors, Virus; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; C482586:BTLA protein, human; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D008565:Membrane Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D011991:Receptors, Virus