Journal article
Aberrant T-Cell Antigen Receptor-Mediated Responses in Autoimmune Lymphoproliferative Syndrome
Clinical immunology (Orlando, Fla.), Vol.104(1), pp.31-39
2002
DOI: 10.1006/clim.2002.5249
PMID: 12139945
Abstract
Autoimmune Lymphoproliferative Syndrome (ALPS) is a disorder of defective lymphocyte apoptosis due to mutations of the Fas receptor and other molecules in the Fas signaling pathway. In addition to accumulation of CD4
− CD8
− double-negative (DN) T cells, many patients display a dysregulated cytokine pattern with dysfunctional T cells, suggesting Fas defects may impact pathways of T-cell activation/differentiation. Here, we report two novel mutations in the Fas receptor resulting in an ALPS phenotype. Utilizing flow cytometry, we found anti-CD3 activated CD4
+ T cells from these patients were incapable of fully upregulating activation markers (CD25, CD69, and CD40L) or producing interferon-γ and IL-2. Additionally, DN T cells were unable to transduce proximal T-cell antigen receptor signals or produce cytokines. Furthermore, DN T cells overexpressed CD57 and phenotypically resembled end-stage effector cells. As DN T cells were essentially anergic, the clinical manifestations of autoimmunity are more likely to be a consequence of aberrant cytokine secretion within the CD4
+ T-cell subpopulation.
Details
- Title: Subtitle
- Aberrant T-Cell Antigen Receptor-Mediated Responses in Autoimmune Lymphoproliferative Syndrome
- Creators
- Frederick D Goldman - Departments of Pediatircs, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Rajeev Vibhakar - Departments of Pediatircs, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Jennifer M Puck - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892Stephen E Straus - National Human Genome Research Institute, National Center for Complementary and Alternative Medicine and Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892Zuhair K Ballas - Medicine, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Clay Hollenback - Departments of Pediatircs, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Thomas Loew - Departments of Pediatircs, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Anthony Thompson - Departments of Pediatircs, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Kejing Song - Pathology, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242Robert T Cook - Pathology, University of Iowa Hospitals and Clinics and Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, Iowa, 52242
- Resource Type
- Journal article
- Publication Details
- Clinical immunology (Orlando, Fla.), Vol.104(1), pp.31-39
- Publisher
- Elsevier Inc
- DOI
- 10.1006/clim.2002.5249
- PMID
- 12139945
- ISSN
- 1521-6616
- eISSN
- 1521-7035
- Language
- English
- Date published
- 2002
- Academic Unit
- Pathology; Immunology; Internal Medicine
- Record Identifier
- 9984094723202771
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