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* Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain;
Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain;
Pediatric Immunology, Uludag University Medical Faculty, Görükle-Bursa, Turkey;
Immunology Division, Hacettepe University Children’s Hospital, Ankara, Turkey;
¶ Inmunología, Hospital 12 de Octubre, Madrid, Spain; and
|| Inmunobiología Molecular, Hospital Gregorio Marañón, Madrid, Spain
The biological role in vivo of the homologous CD3
and 
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 CD3 deficiency and SCID symptoms and compared them with three CD3-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 
and T lymphocytopenia, poor in vitro proliferative responses to Ags and mitogens at diagnosis, and very low TCR rearrangement excision circles and CD45RA+ 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 CD3 (or CD3
) deficiencies are in infants with life-threatening SCID and very severe and T lymphocytopenia. Thus, the peripheral T lymphocyte pool was comparatively well preserved in human CD3 deficiencies despite poor thymus output or clinical outcome. We propose a CD3 >> CD3 hierarchy for the relative impact of their absence on the signaling for T cell production in humans.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Ministerio de Educación y Ciencia (BFU2005-01738/BMC), Fondo de Investigaciones Sanitarias (05/946), Ministerio de Ciencia y Tecnología (BMC2002-3247), Comunidad Autónoma de Madrid (GR/SAL/0570/2004), and Mutua Madrileña. A.C.G. and V.P.-F. were supported by fellowships from the Universidad Complutense de Madrid and Ministerio de Educación y Ciencia, respectively.
2 M.J.R., M.A.M.-P., and S.S.K. are joint first authors.
3 Address correspondence and reprint requests to Dr. José R. Regueiro, Departamento de Inmunología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain. E-mail address: regueiro{at}med.ucm.es
4 Abbreviation used in this paper: TREC, TCR rearrangement excision circle.
This article has been cited by other articles:
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  G. M. Siegers, M. Swamy, E. Fernandez-Malave, S. Minguet, S. Rathmann, A. C. Guardo, V. Perez-Flores, J. R. Regueiro, B. Alarcon, P. Fisch, et al. Different composition of the human and the mouse {gamma}{delta} T cell receptor explains different phenotypes of CD3{gamma} and CD3{delta} immunodeficiencies J. Exp. Med., October 29, 2007; 204(11): 2537 - 2544. [Abstract] [Full Text] [PDF]
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