NDLI: A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ

Content Provider	PubMed Central
Author	Gil, Juana Busto, Elena M. Beatriz, Garcillán Chean, Carmen Cruz, García-rodríguez Maria Andrea, Díaz-alderete Navarro, Joaquín Jesús, Reiné Mencía, Angeles Gurbindo, Dolores Cristina, Beléndez Gordillo, Isabel Marlena, Duchniewicz Höhne, Kerstin Félix, García-sánchez Eduardo, Fernández-cruz Eduardo, López-granados Schamel, Wolfgang W. A. Moreno-pelayo, Miguel A. Recio, María J. Regueiro, José R.
Copyright Year	2011
Abstract	T cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3δ-deficient patients described to date showed a complete block in T cell development. However, CD3δ-KO mice have an αβ T cell–specific defect. Here, we report 2 unrelated cases of SCID with a selective block in αβ but not in γδ T cell development, associated with a new splicing mutation in the CD3D gene. The patients’ T cells showed reduced CD3D transcripts, CD3δ proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant αβ T cells were oligoclonal. T cell–dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of αβ T cells, surface TCR expression was more reduced in γδ than in αβ T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3δ requirements for αβ versus γδ T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.
Related Links	http://dx.doi.org/10.1172/jci44254
Ending Page	3876
Page Count	5
Starting Page	3872
File Format	PDF
ISSN	00219738
e-ISSN	15588238
Journal	The Journal of Clinical Investigation
Issue Number	10
Volume Number	121
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2011-10-03
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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