Severe combined immunodeficiency caused by deficiency in either the d or the e subunit of CD 3

We investigated the molecular mechanism underlying a severe combined immunodeficiency characterized by the selective and complete absence of T cells. The condition was found in 5 patients and 2 fetuses from 3 consanguineous families. Linkage analysis performed on the 3 families revealed that the patients were carrying homozygous haplotypes within the 11q23 region, in which the genes encoding the g, d, and e subunits of CD3 are located. Patients and affected fetuses from 2 families were homozygous for a mutation in the CD3D gene, and patients from the third family were homozygous for a mutation in the CD3E gene. The thymus from a CD3d-deficient fetus was analyzed and revealed that T cell differentiation was blocked at entry into the double positive (CD4+CD8+) stage with the accumulation of intermediate CD4–single positive cells. This indicates that CD3d plays an essential role in promoting progression of early thymocytes toward doublepositive stage. Altogether, these findings extend the known molecular mechanisms underlying severe combined immunodeficiency to a new deficiency, i.e., CD3e deficiency, and emphasize the essential roles played by the CD3e and CD3d subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR. Article Immunology