Inmunodeficiencia selectiva de infocitos tab (tab-tgd b nk )causada por una mutación en el gen cd3d

Laburpena

T cells recognize antigens via their cell surface TCR and are classified as either ab or gd depending on the variable chains in their TCR, a and b or g and d, respectively. Both ab and gd TCRs also contain several invariant chains, including CD3d, wh ich support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect only one lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3d-deficient pat ients described to date showed a complete block in T cell development. However, CD3d-KO mice have an gd T cell¿specific defect. Here, we report two unrelated cases of SCID with a selective block in ab but not in gd T cell development, associated with a new splicing mutation in the CD3D gene. The patients¿ T cells showed reduced CD3D transcripts, CD3d 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 ab 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 gd T cells, surface TCR expression was more r educed in gd than in ab T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3d requirements for ab versus gd 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.