Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n = 60) subgrouped according to the IgHV mutational status (IgHVmut, n = 24; IgHVunmut, n = 36). CD5high subpopulation showed a high percentage of CXCR3 (P < 0.001), CCR10 (P = 0.001), and CD62L (P = 0.031) and high levels of CXCR5 (P = 0.005), CCR7 (P = 0.013) compared to CD5low cells expressing high CXCR4 (P < 0.001). Comparing IgHVmut and IgHVunmut patients, high levels of CXCR3 on CD5high and CD5low subpopulations were detected in the IgHVmut patients, with better discrimination in CD5low subpopulation. Levels of CXCR3 on CD5low subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both CD5high and CD5low neoplastic cells in IgHVmut with a better prognosis compared to IgHVunmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.
- MeSH
- antigeny CD5 metabolismus MeSH
- biologické markery MeSH
- chemotaxe imunologie MeSH
- chronická lymfatická leukemie diagnóza genetika metabolismus terapie MeSH
- imunofenotypizace MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekuly buněčné adheze metabolismus MeSH
- mutace * MeSH
- pohyb buněk MeSH
- prognóza MeSH
- receptory chemokinů metabolismus MeSH
- receptory CXCR3 genetika metabolismus MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- variabilní oblast imunoglobulinu genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
T follicular helper (Tfh) cells are fundamental for B cell selection and antibody maturation in germinal centers. Circulating Tfh (cTfh) cells constitute a minor proportion of the CD4+ T cells in peripheral blood, but their clonotypic relationship to Tfh populations resident in lymph nodes and the extent to which they differ from non-Tfh CD4+ cells have been unclear. Using donor-matched blood and tonsil samples, we investigate T cell receptor (TCR) sharing between tonsillar Tfh cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing reveals considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. Furthermore, influenza-specific cTfh cell clones derived from blood can be found in the repertoire of tonsillar Tfh cells. Therefore, human blood samples can be used to gain insight into the specificity of Tfh responses occurring in lymphoid tissues, provided that cTfh subsets are studied.
- MeSH
- buněčné klony cytologie MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- dárci tkání MeSH
- dospělí MeSH
- folikulární pomocné T-buňky imunologie MeSH
- hemaglutininové glykoproteiny viru chřipky imunologie MeSH
- krční mandle imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- počítačová simulace MeSH
- podskupiny lymfocytů imunologie MeSH
- receptory CXCR3 metabolismus MeSH
- velikost buňky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
In mice, the ability of naive T (TN) cells to mount an effector response correlates with TCR sensitivity for self-derived Ags, which can be quantified indirectly by measuring surface expression levels of CD5. Equivalent findings have not been reported previously in humans. We identified two discrete subsets of human CD8+ TN cells, defined by the absence or presence of the chemokine receptor CXCR3. The more abundant CXCR3+ TN cell subset displayed an effector-like transcriptional profile and expressed TCRs with physicochemical characteristics indicative of enhanced interactions with peptide-HLA class I Ags. Moreover, CXCR3+ TN cells frequently produced IL-2 and TNF in response to nonspecific activation directly ex vivo and differentiated readily into Ag-specific effector cells in vitro. Comparative analyses further revealed that human CXCR3+ TN cells were transcriptionally equivalent to murine CXCR3+ TN cells, which expressed high levels of CD5. These findings provide support for the notion that effector differentiation is shaped by heterogeneity in the preimmune repertoire of human CD8+ T cells.
- MeSH
- aktivace lymfocytů imunologie MeSH
- biologické markery MeSH
- buněčná diferenciace imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie metabolismus MeSH
- dospělí MeSH
- imunofenotypizace MeSH
- imunologická paměť MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- myši MeSH
- receptory CXCR3 metabolismus MeSH
- senioři MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
Objective. To determine the expression of chemokine receptors in lymphocytes from thyroid nodules and peripheral blood in patients with and without Hashimoto's thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid nodules and HT and 60 women with thyroid nodules without HT (controls) who underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes from FNAB samples and from peripheral blood. Results. The percentage of CRTH2+ lymphocytes was higher in nodules with HT in comparison with controls, both in FNAB samples (13.95 versus 6.7%, p = 0.008) and in peripheral blood (6.7 versus 5.13%, p = 0.047), and positively correlated with serum antibodies to thyroid peroxidase (r = 0.243; p = 0.026) and negatively correlated with thyroid volume (r = -0.346; p = 0.008). Lymphocytes from neoplastic nodules showed a higher expression of both CXCR3 and CCR5 than those from hyperplastic ones. Conclusion. Flow cytometry performed in FNAB samples may serve as a good tool in investigation of intrathyroidal expression of immunological parameters. In our study, the CRTH2 expression on thyroid-infiltrating lymphocytes as well as on lymphocytes from peripheral blood was increased in HT as compared to controls.
- MeSH
- biologické markery MeSH
- cytokiny metabolismus MeSH
- dospělí MeSH
- exprese genu MeSH
- Hashimotova nemoc diagnóza imunologie MeSH
- imunofenotypizace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty imunologie metabolismus patologie MeSH
- receptory CCR5 genetika metabolismus MeSH
- receptory CXCR3 genetika metabolismus MeSH
- receptory imunologické genetika metabolismus MeSH
- receptory prostaglandinů genetika metabolismus MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tenkojehlová biopsie MeSH
- ultrasonografie MeSH
- uzle štítné žlázy diagnóza imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- exprese genu * MeSH
- lidé MeSH
- messenger RNA MeSH
- proteiny T-boxu MeSH
- receptory CXCR3 MeSH
- sarkoidóza * MeSH
- Th1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
- práce podpořená grantem MeSH
Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
- MeSH
- bronchoalveolární lavážní tekutina chemie cytologie MeSH
- chemokin CCL5 genetika metabolismus MeSH
- dospělí MeSH
- exprese genu MeSH
- interferon gama genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické uzliny metabolismus MeSH
- messenger RNA metabolismus MeSH
- plíce metabolismus MeSH
- plicní sarkoidóza genetika imunologie metabolismus MeSH
- proteiny T-boxu metabolismus MeSH
- receptory chemokinů genetika metabolismus MeSH
- receptory CXCR3 genetika metabolismus MeSH
- receptory interleukinu-2 genetika metabolismus MeSH
- Th1 buňky imunologie metabolismus MeSH
- upregulace MeSH
- virové receptory genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sarcoidosis and extrinsic allergic alveolitis (EAA) are granulomatous lung diseases with predominantly Th1 immune response. In this prospective study, the authors analyzed the expression of chemokine receptors CXCR2, CXCR3, and CCR3 on bronchoalveolar lavage fluid (BALF) CD4 T cells of patients either with EAA or sarcoidosis. The authors investigated the correlation of chemokine receptors expression, lymphocyte and neutrophil counts in BALF, and high-resolution tomography (HRCT) pattern. Thirteen sarcoidosis and 6 EAA patients were enrolled in the study. The expression of chemokine receptors on BALF CD4 T cells were analyzed by flow cytometry. HRCT scoring system according to Kazerooni was used for evaluation of the disease extent. The authors have found positive correlation between BALF CD4 T-cell CXCR3 expression and HRCT alveolar score in EAA patients (P <. 01). CXCR2 expression on BALF CD4 T cells and interstitial HRCT score did not show a correlation either in the EAA or the sarcoidosis group. Positive correlation between CCR3 expression on CD4+ T cells and HRCT interstitial score was proven in the EAA group (P <. 05). The authors conclude that Th2 predominant immune response may play an important role in chronic EAA pathogenesis. The role of chemokine receptors in the pathogenesis of EAA and sarcoidosis should be presumed and investigated.
- MeSH
- bronchoalveolární lavážní tekutina cytologie imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie patologie MeSH
- dospělí MeSH
- hypersenzitivní pneumonitida imunologie patologie radiografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní sarkoidóza imunologie patologie radiografie MeSH
- počítačová rentgenová tomografie MeSH
- prospektivní studie MeSH
- receptory CCR3 metabolismus MeSH
- receptory chemokinů metabolismus MeSH
- receptory CXCR3 metabolismus MeSH
- receptory interleukinu-8B metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Multiple sclerosis (MS) usually develops in young adults with a complex predisposing genetic background. Polymorphisms in the gene for chemokine receptor CCR5 have been proposed to confer susceptibility to or protection from MS. Study of molecules participating in the inflammatory process contributed to the development of a new humanized monoclonal antibody, natalizumab, aimed at the adhesive molecule VLA-4. Natalizumab (Biogen Idec/Elan) went through successful clinical studies and its clinical testing was also carried out in the Czech Republic. Twenty-one patients with MS were included in the AFFIRM study (2-year, placebo-controlled study and consecutive 7-month unblinded natalizumab treatment); immunophenotyping of the cerebrospinal fluid (CSF)- CD4+CCR5+CXCR3+ lymphocytes, using flow cytometer FACSCalibur and monoclonal antibodies (BD Biosciences), was done at the end of natalizumab treatment and 1 year after the therapy withdrawal. Compared to MS patients receiving other therapy, the patients treated with natalizumab had statistically significantly (P < 0.0001) higher levels of CCR5+ and lower levels of CD4+ T lymphocytes in CSF, whereas the levels of CXCR3+ lymphocytes were almost the same as in other patients. CCR5-positive CSF lymphocytes decreased 1 year after treatment withdrawal. Natalizumab treatment alters the percentage of CCR5+ and CD4+ cells in CSF. In view of the excellent temporary clinical results of the therapy, which are yet to be assessed in the course of a longer time period, our results show a possible explanation for the therapeutic success of this drug as well as for the development of progressive multifocal leukoencephalopathy.
- MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus účinky léků MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- receptory CCR5 metabolismus MeSH
- receptory CXCR3 metabolismus MeSH
- roztroušená skleróza farmakoterapie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- chemokin CXCL10 fyziologie MeSH
- dermatomyozitida * diagnóza patologie MeSH
- exprese genu MeSH
- geny MHC třídy I fyziologie MeSH
- imunohistochemie MeSH
- interferon beta fyziologie MeSH
- interpretace statistických dat MeSH
- jehlová biopsie MeSH
- lidé MeSH
- polymyozitida * diagnóza patologie MeSH
- receptory CXCR3 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
