Tumor Necrosis Factor Receptor 2 (TNFR2) expression is increasingly being linked to tolerogenic immune reactions and cells with suppressor function including a subset of T-regulatory cells. B-regulatory cells play an important role in control of T-cell responses and inflammation. Recently, we described TNFR2 as a marker for IL-10-producing B cells, a hallmark of this cell subset. Here, we demonstrate that proliferation of T cells is reduced in the presence of TNFR2 positive human memory B cells generated with TLR9 ligand, while TNFR2- and TNFR2+CD27- B cells display costimulatory activity. Our data further reveal that IL-10 secretion is characteristic of IgM+ naïve and memory B cells but suppressive activity is not restricted to IL-10: (i) the inhibitory effect of TNFR2+ switched memory B cells was comparable to that exerted by TNFR2+ IgM+ memory B cells although IL-10 secretion levels in the cocultures were lower; (ii) supernatants from TNFR2+ memory B cells failed to suppress T-cell proliferation. Based on our findings, we propose that formation of Breg is a specific characteristic of human memory B cells undergoing terminal differentiation. Our data further corroborate that TNFR2 represents a viable marker for identification of memory B cells with regulatory function.

• MeSH
• aktivace lymfocytů genetika   imunologie   MeSH
• B-lymfocyty imunologie   metabolismus   MeSH
• běžná variabilní imunodeficience etiologie   metabolismus   MeSH
• buněčná diferenciace imunologie   MeSH
• cytokiny metabolismus   MeSH
• imunologická paměť * MeSH
• imunomodulace genetika   MeSH
• interleukin-10 metabolismus   MeSH
• lidé MeSH
• mezibuněčná komunikace imunologie   MeSH
• receptory TNF - typ II genetika   metabolismus   MeSH
• regulace genové exprese * MeSH
• regulační B-lymfocyty imunologie   metabolismus   MeSH
• studie případů a kontrol MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• toll-like receptor 9 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Cytomegalovirus (CMV) infection is a life-threatening complication after solid organ transplantation. It usually appears in the first months after transplantation as a consequence of immunosuppression. The goal of this study was to evaluate the clinical significance of CD38(high)/CD3(+)8(+) percentages in the detection of CMV infection in patients after kidney transplantation. METHODS: In this retrospective study, 269 patients were monitored 2-3 months after renal transplantation for the percentage of CD38(high)/CD3(+)8(+) lymphocytes estimated by flow cytometry and for the number of CMV DNA copies in peripheral blood using a real-time polymerase chain reaction. RESULTS: CMV infection was diagnosed in 12 (4.5%) patients between the 31st and 63rd days after transplantation, and all of them had percentages of CD38(high)/CD3(+)8(+) T lymphocytes above 20%. In 4 of them, CMV DNAemia in peripheral blood was not detected, and 2 of these suffered from tissue-invasive CMV disease. In 7 patients with CMV DNAemia, the CD38(high)/CD3(+)8(+) T lymphocyte percentage did not exceed 20%, and these patients did not develop CMV infection requiring antiviral treatment. In 23 additional patients, a CD38(high)/CD3(+)CD8(+) percentage above 20% was recorded without CMV DNAemia. All of the remaining 234 patients never exceeded the arbitrary limit of 20%. The estimated sensitivity and specificity were 100% and 91% using clinical decision on the presence of CMV infection as a reference value, respectively. The estimated negative predictive value was 100%; however, the estimated positive predictive value was quite low (34%). CONCLUSIONS: The CD38(high)/CD3(+)8(+) lymphocyte percentage seems to be a useful additional diagnostic marker for CMV infection in patients after kidney transplantation, especially when patients are in the risk of a tissue-invasive disease when CMV DNA copies may not be detectable in peripheral blood.

• MeSH
• antigeny CD38 biosyntéza   MeSH
• biologické markery metabolismus   MeSH
• CD8-pozitivní T-lymfocyty imunologie   metabolismus   patologie   MeSH
• cytomegalovirové infekce komplikace   diagnóza   imunologie   MeSH
• Cytomegalovirus patogenita   fyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování fyziologických funkcí metody   MeSH
• prediktivní hodnota testů MeSH
• rejekce štěpu komplikace   diagnóza   imunologie   MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• transplantace ledvin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH