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| Status |
Public on Sep 26, 2008 |
| Title |
Impaired T-cell function in patients with novel ICOS |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Interaction of ICOS - ICOS ligand is required for the germinal center formation, T-cell immune responses, and development of autoimmune diseases. Human ICOS deficiency with the identical ICOS mutation has been identified in nine patients worldwide. In vitro studies showed T-cell defect of the patients was mild, and in vivo autoimmunity was uncommon and mild. Here we report in-depth analysis of T-cell function in two siblings with novel ICOS deficiency. While the brother displayed mild skin infections, psoriasis-like skin region, and defective immunoglobulin class switching, the sister had more severe symptoms, which included immunodeficiency, rheumatoid arthritis, inflammatory bowel disease, interstitial pneumonitis, and psoriasis. Despite of normal CD3/CD28-induced proliferation and IL-2 production in vitro, peripheral blood T-cells from both patients demonstrated decreased percentage of CD4 central and effector memory T-cells and impaired production of Th1, Th2, and Th17 cytokines upon CD3/CD28 costimulation or upon PMA/ionophore stimulation. The defective polarization into effector cells were associated with impaired induction of T-bet, GATA3 and MAF and RORC. Reduced CTLA-4+CD45RO+ FoxP3+ regulatory T-cells and diminished induction of inhibitory cell surface molecules including CTLA-4 were also observed in the patients. Further analysis of the gene expression and immune functions of the patients demonstrated increased induction of RANKL, lack of IFN-g response, and loss of Itch expression upon activation in the female case with autoimmunity. Our study suggests extensive T-cell dysfunction and loss of balance between effector cells and regulatory cells in the ICOS-deficient patients may account for their immunodeficiency and/or autoimmune disorder.
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| Overall design |
One control and two patients samples. Negatively-selected CD4 T-cells were incubated with or without stimulants (plate-bound anti-CD3mAb and anti-CD28mAb). The cells were collected at 24h time point.
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| Contributor(s) |
Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, Azuma M, Sang-Kyou L, Mizutani S, Tomohiro M |
| Citation(s) |
19380800 |
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| Submission date |
Sep 22, 2008 |
| Last update date |
Mar 25, 2019 |
| Contact name |
naomi takahashi |
| E-mail(s) |
takanao.ped@tmd.ac.jp
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| Phone |
+81-3-5803-5245
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| Fax |
+81-3-5803-5245
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| Organization name |
Tokyo Medical and Dental University
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| Department |
Department of Pediatrics and Developmental Biology
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| Street address |
1-5-45 Yushima
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| City |
Bunkyo-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
113-8510 |
| Country |
Japan |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA111055 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12875_RAW.tar |
52.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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