title: CD3 delta immunodeficiency.
abstract: OBJECTIVE
  The review describes advances in understanding the role of the CD3 delta subunit in human T-cell development as deduced from a recently described human immunodeficiency. The review also compares CD3 delta deficiency with other human CD3 subunit deficiencies and with corresponding animal models.
  
  
  RESULTS
  In describing CD3 delta deficiency in humans this review shows that patients with profound T-cell depletion, who present at 2-3 months with severe viral infection, lack CD3 delta as a result of a mutation in the extracellular domain of this gene. The genetic aberration was discovered by comparing patients' and normal thymocytes, using mass gene screening with the microarray technique. In humans the absence of CD3 delta results in a complete arrest in thymocyte development at the stage of double negative to double positive transition and the development of gamma delta T-cell receptor-positive T cells is also impaired.
  
  
  CONCLUSIONS
  Unlike patients with CD3 gamma or CD3 epsilon deficiency who have a milder condition, patients with CD3 delta deficiency present with severe lethal susceptibility to infections during early infancy. As expected, this profound immunodeficiency was cured with an allogenic bone marrow transplantation. In contrast to murine CD3 (-/) delta, which retains a normal gamma delta T-cell receptor-positive T-cell population and only partly affects the developmental transition of double positive to single positive thymocytes, CD3 delta in humans appears to be more critically required for the development of both alpha beta and gamma delta T-cell receptor-positive T-cell lineages. The studies also show for the first time that comparing relevant patients' with normal tissue using microarray technology can aid in the discovery of the genetic basis of inherited disorders.
authors.affiliation: Division of Immunology and Allergy, and Program of Infection, Immunity, Injury and Repair, The Hospital for Sick Children and The University of Toronto, Ontario M5G 1X8, Canada. chaim.roifman@sickkids.ca
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005820:Genetic Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C115335:CD3E protein, human; C472562:CD3delta antigen