Expert Reviews in Molecular Medicine

 


Review Article

T-cell signalling and immune system disorders

Beverley Wilkinson a1, Jocelyn S. Downey a1 and Christopher E. Rudd a1c1
a1 Molecular Immunology Section, Department of Immunology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

Abstract

T-cell receptor (TCR) engagement initiates intracellular signalling cascades that lead to T-cell proliferation, cytokine production and differentiation into effector cells. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions. The integration of these signals is essential for the normal development, homeostasis and function of T cells. Defects in a single mediator can produce T cells that are unable to participate fully in an immune response and/or that mount an inappropriate response, which leads to immunodeficiency, autoimmunity or leukaemia/lymphomas. This review highlights some of the key players in T-cell signalling and their involvement in the development of various clinical disease states. Some of these immune-specific signalling proteins are attractive potential targets in the development of therapies to augment T-cell responses to antigen or tumours, and to treat immune cell disorders.


Key Words: T cell; kinase; adaptor; phosphatase; immunodeficiency; autoimmunity.

Correspondence:
c1 Molecular Immunology Section, Department of Immunology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. Tel: +44 (0)20 8383 8421; Fax: +44 (0)20 8383 8434; E-mail: c.rudd@imperial.ac.uk