title: Differential biological role of CD3 chains revealed by human immunodeficiencies.
abstract: The biological role in vivo of the homologous CD3gamma and delta invariant chains within the human TCR/CD3 complex is a matter of debate, as murine models do not recapitulate human immunodeficiencies. We have characterized, in a Turkish family, two new patients with complete CD3gamma deficiency and SCID symptoms and compared them with three CD3gamma-deficient individuals belonging to two families from Turkey and Spain. All tested patients shared similar immunological features such as a partial TCR/CD3 expression defect, mild alphabeta and gammadelta T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA(+) alphabeta T cells. However, intrafamilial and interfamilial clinical variability was observed in patients carrying the same CD3G mutations. Two reached the second or third decade in healthy conditions, whereas the other three showed lethal SCID features with enteropathy early in life. In contrast, all reported human complete CD3delta (or CD3epsilon) deficiencies are in infants with life-threatening SCID and very severe alphabeta and gammadelta T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3gamma deficiencies despite poor thymus output or clinical outcome. We propose a CD3delta >> CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans.
authors.affiliation: Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Recio
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno-Pelayo
authors.forename: Sara S
authors.initials: SS
authors.lastname: Kiliç
authors.forename: Alberto C
authors.initials: AC
authors.lastname: Guardo
authors.forename: Ozden
authors.initials: O
authors.lastname: Sanal
authors.forename: Luis M
authors.initials: LM
authors.lastname: Allende
authors.forename: Verónica
authors.initials: V
authors.lastname: Pérez-Flores
authors.forename: Angeles
authors.initials: A
authors.lastname: Mencía
authors.forename: Silvia
authors.initials: S
authors.lastname: Modamio-Høybjør
authors.forename: Elena
authors.initials: E
authors.lastname: Seoane
authors.forename: José R
authors.initials: JR
authors.lastname: Regueiro
mesh_terms: D000328:Adult; D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D009154:Mutation; D010375:Pedigree; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D013030:Spain; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014421:Turkey
chemical_list: D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C472562:CD3delta antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017493:Leukocyte Common Antigens