Severe combined immunodeficiency with absence of peripheral blood CD8+ T cells due to ZAP-70 deficiency.
During ontogeny, T lymphocytes are selected for CD4 or CD8 expression in part by their ability to signal properly through the TCR. Transmission of such signals requires the activation of specific cytoplasmic protein tyrosine kinases (PTKs) which lead to T-cell activation through poorly understood mechanisms. Recently, mutations in one such PTK, called ZAP-70, have been shown to be responsible for a rare, autosomal recessive form of severe combined immunodeficiency (SCID) in humans. This distinctive SCID syndrome is characterized by the selective absence of peripheral CD8+ T cells and by abundant circulating CD4+ T cells that fail to respond to TCR-mediated stimuli in vitro. In this report, we describe in detail the clinical and laboratory findings in one patient with ZAP-70 deficiency and discuss the insights provided by this disorder into the pathways of TCR signal transduction and T-cell development.
Elder
M E
ME
Department of Pediatrics, University of California, San Francisco 94143, USA.
Hope
T J
TJ
Parslow
T G
TG
Umetsu
D T
DT
Wara
D W
DW
Cowan
M J
MJ
D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000097:blood / Q000172:deficiency*; D011518:Proto-Oncogene Proteins / Q000097:blood; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency; D016511:Severe Combined Immunodeficiency / Q000097:blood*; D051746:ZAP-70 Protein-Tyrosine Kinase
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human