Clinical experience in T cell deficient patients

This review will discuss recent progress in our clinical and molecular understanding of a variety of disorders including: severe combined immunodeficiency, specific T cell immunodeficiencies, signaling defects, DNA repair defects, immune-osseous dysplasias, thymic disorders and abnormalities of apoptosis.There is still much to discover in this area and some conditions which are as yet very poorly understood. However, with increased knowledge about how these disorders can present and the particular problems each group may face it is hoped that these patients can be recognized early and managed appropriately, so providing them with the best possible outcome.T cell disorders have been poorly understood until recently. Lack of knowledge of underlying molecular mechanisms together with incomplete data on long term outcome made it difficult to assess prognosis and give the most effective treatment. Rapid progress in defining molecular defects, greatly improved supportive care and much improved results from hematopoietic stem cell transplantation (HSCT) now mean that curative treatment is possible for many patients. However, this depends on prompt recognition, accurate diagnosis and careful treatment planning by experienced immunologists. Through discussion of many key T cell disorders such as: severe combined immunodeficiency, other T cell disorders, thymic disorders and disorders of lymphocyte apoptosis we hope this review will aid this process.Severe Combined Immunodeficiency (SCID) describes a heterogeneous group of genetically determined conditions which result in lymphopenia and hypogammaglobulinemia, with inability to fight infection and early death. Four main mechanism result in SCID: defective cytokine dependent signaling in T cell pre-cursors, defective V(D)J rearrangement, defective pre-TCR or TCR signaling and premature cell death due to accumulation of purine metabolites. The most common form of SCID is the X-linked form due to mutations in genes coding for th