Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25+ cells and thus they potently expand Treg cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice. We demonstrate here that this phenomenon is dependent on endogenous IFN-γ and T cells, as it is not manifested in IFN-γ deficient and nude mice, respectively. Administration of IL-2/JES6 leads to the emergence of CD25+Foxp3-CD4+ and CD25+Foxp3-CD8+ T cells producing IFN-γ in various organs, particularly in the liver. IL-2/JES6 also increase counts of CD11b+CD14+ cells in the blood and the spleen with higher sensitivity to LPS in terms of TNF-α production and induce expression of CD25 in these cells. These findings indicate safety issue for potential use of IL-2/JES6 or similar IL-2-like immunotherapeutics.

• MeSH
• interferon gama nedostatek   MeSH
• interleukin-2 metabolismus   MeSH
• lipopolysacharidy metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši nahé MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Perivascular epithelioid cell tumors (PEComas) are rarely found in the urinary tract. The clinicopathologic characteristics of 10 cases, retrospectively collected from 5 medical institutions in 3 different European countries, are presented in this study. Male/female ratio was 3:7 and the average age at diagnosis was 62.7 years. Nine cases were sporadic and 1 showed germline mutation of the TSC2 gene. Eight cases were located in the kidney, 1 in the left adrenal and 1 in the right ureter. All of the patients were alive and free of disease at the time of last contact (mean follow-up, 14.1 mo). Four cases displayed a conventional morphology and 6 showed a prominent sclerotic stroma. By immunohistochemistry, melanocytic markers were consistently expressed, especially HMB-45 (10 cases), MiTF (9 cases), and Melan-A (6 cases). Desmin was expressed in 6 cases; 2 cases were positive for CD117; a single case showed TFE3 expression. pMAPK, mTOR, and pAKT demonstrated variable immunostaining with focal positivity in 7, 4, and 2 cases, respectively. Cytokeratins were repeatedly negative in all cases. PEComas in the urinary tract, especially in the renal region, may show a relatively high frequency of the sclerosing histologic subtype. Knowledge of the distinct histology and immunohistochemical profile is vital to correctly diagnose this rare entity.

• MeSH
• angiomyolipom genetika   patofyziologie   MeSH
• benigní fibrózní histiocytom genetika   patofyziologie   MeSH
• cystická onemocnění ledvin genetika   patofyziologie   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• interferon gama nedostatek   genetika   MeSH
• kinasy ribozomálního proteinu S6, 70-kDa metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• močové ústrojí patofyziologie   MeSH
• nádory z perivaskulárních epiteloidních buněk genetika   patofyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• signální transdukce genetika   MeSH
• TOR serin-threoninkinasy genetika   metabolismus   MeSH
• transkripční faktory BHLH-Zip genetika   metabolismus   MeSH
• tuberózní skleróza genetika   patofyziologie   MeSH
• urologické nádory genetika   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH