Phenotypic features of selective T cell deficiency characterized by absence of CD8+ T lymphocytes and undetectable mRNA for ZAP-70 kinase.
Selective T cell deficiency is a rare immune deficiency characterized by the absence of CD8+ T lymphocytes and depressed/absent T cell function. This syndrome has been associated with mutations in the gene for ZAP-70, a tyrosine kinase that has profound effects on signaling via the T cell receptor. In this paper we describe a patient with selective T cell deficiency and certain phenotypic features that are unique among the small number of patients described. The patient had virtually absent T cell function, hypogammaglobulinemia, and no response to vaccination. The T lymphocytes failed to respond to mitogenic stimuli, even in the presence of exogenous interleukin 2. Similar to other patients with this disorder, the T cells were capable of proliferating when stimulated by pharmacologic agents such as phorbol ester and ionomycin. While peripheral blood T cells had limited capability to increase cytosolic Ca2+ levels in response to mitogenic stimulation, thymocytes responded to a large panel of antibodies and mitogens. This report broadens the spectrum of clinical presentations associated with selective T cell deficiency and, for the first time, compares the responses of both peripheral T cells and thymocytes. The data support the concept that the defect in signal transduction resulting from the absence of ZAP-70 is primarily manifested following export of T lymphocytes from the thymus and that selection of CDS-positive T cells is dependent on the presence of ZAP-70.
Mazer
B
B
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Harbeck
R J
RJ
Franklin
R
R
Schwinzer
R
R
Kubo
R
R
Hayward
A
A
Gelfand
E W
EW
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002118:Calcium / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology; D018655:Lymphocyte Count; D008297:Male; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D051746:ZAP-70 Protein-Tyrosine Kinase
D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D002118:Calcium