scholarly journals Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes

2018 ◽  
Vol 51 (3) ◽  
pp. 1701124 ◽  
Author(s):  
Caroline E. Broos ◽  
Laura L. Koth ◽  
Menno van Nimwegen ◽  
Johannes C.C.M. in ‘t Veen ◽  
Sandra M.J. Paulissen ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Pulmonary Sarcoidosis ◽  
Mediastinal Lymph Nodes ◽  
T Helper ◽  
Peripheral Blood Mononuclear

The lung-draining mediastinal lymph nodes (MLNs) are currently widely used to diagnose sarcoidosis. We previously reported that T-helper (Th) 17.1 cells are responsible for the exaggerated interferon-γ production in sarcoidosis lungs. In this study, we aimed to investigate 1) whether Th17.1 cells are also increased in the MLNs of sarcoidosis patients and 2) whether frequencies of the Th17.1 cells at diagnosis may correlate with disease progression.MLN cells from treatment-naive pulmonary sarcoidosis patients (n=17) and healthy controls (n=22) and peripheral blood mononuclear cells (n=34) and bronchoalveolar lavage fluid (BALF) (n=36) from sarcoidosis patients were examined for CD4+ T-cell subset proportions using flow cytometry.Higher proportions of Th17.1 cells were detected in sarcoidosis MLNs than in control MLNs. Higher Th17.1 cell proportions were found in sarcoidosis BALF compared with MLNs and peripheral blood. Furthermore, BALF Th17.1 cell proportions were significantly higher in patients developing chronic disease than in patients undergoing resolution within 2 years of clinical follow-up.These data suggest that Th17.1 cell proportions in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and could serve as a new therapeutic target.

Frequency and Phenotype of T Helper 17 Cells in Peripheral Blood and Synovial Fluid of Patients with Reactive Arthritis

2010 ◽  
Vol 37 (10) ◽  
pp. 2096-2099 ◽  
Author(s):  
HUI SHEN ◽  
JANE C. GOODALL ◽  
J.S. HILL GASTON
Keyword(s):  
Synovial Fluid ◽  
Peripheral Blood ◽  
Reactive Arthritis ◽  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Peripheral Blood Mononuclear ◽  
Color Flow

Objective.To analyze the frequency and phenotype of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cell (SFMC) T helper (Th)17 cells in reactive arthritis (ReA).Methods.T cell surface phenotype and cytokine production were measured following stimulation, using 8-color flow cytometry.Results.The percentages of interleukin 17 (IL-17)–positive CD4+ T cells were increased in SFMC of patients with ReA compared with PBMC. All IL-17+ cells were CD4+CD45RO+; in SFMC most expressed CCR6, but only 50% expressed CCR4. IL-17+ cells sometimes coexpressed IL-22 and/or interferon-γ, but not IL-10.Conclusion.These data support the hypothesis that Th17 cells are involved in ReA pathogenesis.

scholarly journals Minor H Antigen HA-1–specific Regulator and Effector CD8+ T Cells, and HA-1 Microchimerism, in Allograft Tolerance

2004 ◽  
Vol 199 (7) ◽  
pp. 1017-1023 ◽  
Author(s):  
Junchao Cai ◽  
Junglim Lee ◽  
Ewa Jankowska-Gan ◽  
Richard Derks ◽  
Jos Pool ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Renal Allograft ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Severe Combined Immunodeficiency ◽  
Interferon Γ ◽  
T Cell Subsets ◽  
Delayed Type Hypersensitivity ◽  
Peripheral Blood Mononuclear

The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1H peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1–specific CD8+ T cell subsets. The one that stained dimly had the characteristics of a T regulatory (TR) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) β. These HA-1–specific TR cells coexisted with bright tetramer-binding CD8+ T effector (TE) cells. The CD8+ TE cells mediated HA-1–specific DTH and produced interferon-γ. Suppression of these TE functions by TR cells was TGFβ, IL-10, and cytotoxic T lymphocyte–associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8+ memory TR and TE cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.

Cytotoxic T-Cell Response to the Cancer Testis Antigen PASD1 In Multiple Myeloma: PASD1 Peptides for a Generic Vaccine to Treat PASD1-Positive Haematological Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4294-4294
Author(s):  
Andrew J Campbell ◽  
Kamel Ait-Tahar ◽  
Suketu D. Patel ◽  
Martin Barnardo ◽  
Amanda P Liggins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Normal Tissue ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Cancer Testis

Abstract Abstract 4294 Multiple myeloma (MM) is a bone marrow localized plasma cell tumor comprising 1% of all cancers and 10–15% of hematological malignancies. Despite significant advances in treatment, such as bortezomib, patients currently only have a 5-year survival rate of approximately 35%. The identification of improved therapeutic options therefore remains a priority. There is increasing evidence for a role of the immune system in tumor progression. Examples include the remission of some leukemias and lymphomas in immunocompetent patients while allogeneic stem cell transplantation also has a graft-versus-tumor effect in MM. The immunotherapeutic targeting of tumor-associated antigens (TAAs) on MM cells therefore represents an important approach for improved treatment of this disease. MM cells express a number of TAAs, of which cancer testis antigens (CTAs) are of particular interest. Their restricted normal tissue distribution combined with widespread expression in tumors makes them attractive immunotherapeutic targets whilst minimizing potential problems with autoimmunity. Reports of cytotoxic T cells (CTLs, the major effector cells in tumor immunity) and CD4-positive T-helper cells recognizing the NY-ESO-1 and MAGE CTAs in patients with MM suggests the presence of a spontaneous immune response to these molecules, which can be boosted through vaccination with CTAs such as NY-ESO-1. We previously identified PAS (Per ARNT Sim) domain containing 1 (PASD1) protein as a novel diffuse large B-cell lymphoma (DLBCL)-associated CTA. Importantly, PASD1 has a restricted normal tissue distribution but is present in a range of hematological malignancies, including MM. Subsequent in vitro studies have identified immunogenic PASD1 peptides that elicit PASD1-driven CTL or CD4-positive T-helper responses in peripheral blood mononuclear cells from DLBCL patients. Studies using a pre-clinical in vivo murine model have confirmed the immunogenicity of the PASD1 CTL peptides. These critical steps support the use of PASD1 as a potential immunotherapeutic target in DLBCL. The current study was performed to ascertain whether the PASD1 CTL peptides were immunogenic in MM patients and thus have utility for immunotherapy in this disease. Blood samples were obtained from 9 post-treatment myeloma patients attending the John Radcliffe Hospital following informed consent. Peripheral blood mononuclear cells were incubated with the PASD1 CTL peptides PASD1(1)38-47 (QLLDGFMITL) and PASD1(2)167-175 (YLVGNVCIL). A gamma-interferon ELISPOT release assay was performed after 8–10 days. The results are summarized in Table 1.Table 1:Gamma-IFN response to PASD1 in patients with MM.PatientsMHC Class I*Gamma-IFN response to peptides/50,000 cellsPASD1(1)PASD1(2)HIV-1PHADSA*0201+2+/−112+/−41+/−1100+/−14MWA*0201+52+/−244+/−220+/−266+/−8DMA*0201− A*2601+28+/−246+/−68+/−298+/−10JBA*0201+0+/−00+/−02+/−088+/−12JYA*0201+–––72+/−10DAA*0201−2+/−20+/−00+/−082+/−10GGA*0201−58+/−268+/−244+/−288+/−10MDA*0201−52+/−228+/−242+/−292+/−12RSA*0201––––*Results were considered positive if the number of spots in the test wells were at least twice that found in the irrelevant HIV-1 cultures. A significant gamma-interferon response was detected to one or both of the PASD1 peptides in 2/4 A*0201-positive evaluable patients. Analysis of the SYPETHI web-based algorithm predicted the PASD1 peptides used here to be immunogenic in the context of A*2601 and this was confirmed in the one A*2601+ patient studied here. No significant response was detected in the 3 A*0201 and A*2601-negative patients. Double immunolabeling studies using antibodies to PASD1 and CD138 showed PASD1 to be present in a subset of tumor cells in all 7 patients with evaluable ELISPOT data. Our findings demonstrate the immunogenicity of both the PASD1(1) and PASD1(2) peptides in patients with MM. These ‘generic’ peptides therefore represent vaccine candidates for inclusion in a vaccine targeting multiple PASD1-positive hematological malignancies. Disclosures: Banham: University of Oxford: Patents & Royalties. Pulford:Leukaemia and Lymphoma Research: Patents & Royalties.

Sign in / Sign up

Export Citation Format

Share Document