The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat‐shock protein 60 capable of producing the regulatory cytokine interleukin‐10

Kleer, Ismé M. de; Kamphuis, Sylvia; Rijkers, Ger T.; Scholtens, L.; Gordon, Grace; Jager, Wilco de; Häfner, R.; Zee, R. van de; Eden, Willem van; Kuis, Wietse; Prakken, Berent J.

doi:10.1002/art.11174

Cited by 120 publications

(86 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Earlier studies in patients with JIA and patients with RA, using whole Hsp60 proteins, suggested that T cell recognition of human Hsp60 is associated with a regulatory phenotype (26,29,31). Interestingly, in our study, the human Hsp60 epitopes also induced a more antiinflammatory T cell response, as depicted by marked changes in the IL-10:TNF␣ ratio.…”

Section: Discussionsupporting

confidence: 62%

“…Second, in RA, as well as in juvenile idiopathic arthritis (JIA), Hsp60 of microbial origins as well as those of endogenous origins are targets of immune responses (26,27). In the spontaneous remitting form of JIA (oligoarticular JIA), T cells reactive to self Hsp60 at the onset of disease are associated with disease remission (28) and have a striking regulatory phenotype (29). In RA, T cells stimulated with human Hsp60 display a marked suppressive phenotype, compared with T cells stimulated with homologous mycobacterial Hsp65 (26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis

Jong¹,

Lafeber²,

Jager³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan-DR-binding Hsp60-derived epitopes as possible modulators of autoimmune inflammation in RA.Methods. Lymphocyte proliferation assays (using 3 H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls. Results. A disease (RA)-specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4؉ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5-10-fold higher IL-10:TNF␣ ratio, compared with that of the microbial peptides.Conclusion. These results suggest a diseasespecific immune-modulatory role of epitope-specific T cells in the inflammatory processes of RA. Therefore, these pan-DR-binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy.

show abstract

Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis

Jong¹,

Lafeber²,

Jager³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…In addition, CD30 signaling has been found to limit the proliferative potential of autoreactive CD8 effector T cells and protects against autoimmunity in murine models (20). In a human setting, the expression of CD30 (14), and the presence of CD30 þ T cells in synovial fluid has been correlated with a more favorable course in patients with juvenile arthritis (29). These data support the involvement of CD30 in the negative control of immune responses directed against self-antigens, a setting largely including tumor-specific T cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

et al. 2014

View full text Add to dashboard Cite

Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients. Biopsies from positive nodes were selected for comparable tumor infiltration, presence or absence of further regional node metastases, and relapse at 5-year follow-up. Unsupervised analysis of gene expression profiles revealed immune response to be a major gene ontogeny represented. Among genes upregulated in patients with progressing disease, the TNF receptor family member CD30/TNFRSF8 was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30 þ lymphocytes in nodes from progressing patients compared with nonprogressing patients. Phenotypic profiling demonstrated that CD30 þ lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4 þ Foxp3 þ or PD1 þ subpopulations and CD4 À CD8 À T cells. CD30 þ T lymphocytes were increased in peripheral blood lymphocytes of melanoma patients at advanced disease stages. Our findings reinforce the concept that sentinel nodes act as pivotal sites for determining progression patterns, revealing that the presence of CD30 þ lymphocytes at those sites associate positively with melanoma progression. Cancer Res; 74(1); 130-40. Ó2014 AACR.

show abstract

“…Lymphocyte cell surface markers At day 7 from the direct cell culture assays as described above, PBMC were harvested and prepared for fluorescenceactivated cell sorting (FACS) staining as described previously (de Kleer et al 2003). The cells were incubated in 50 μl FACS buffer containing three appropriately diluted phycoerythrin (PE)-, fluorescein isothiocyanate (FITC)-, or Cy-Chromelabeled monoclonal antibodies against human CD4 (clone RPA-T4), CD25 (clones: activated protein C [APC], M-A251; PE, 2A3), CD30 (clone: Ber-H83), and CD69 (clone: FN50).…”

Section: Multiplexed Particle-based Immunoassaymentioning

confidence: 99%

Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis

Kapitein

Aalberse

Klein

et al. 2013

Cell Stress and Chaperones

View full text Add to dashboard Cite

Heat shock protein 60 (hsp60) is a highly conserved stress protein and target of self-reactive T cells in various inflammatory diseases. Not much is known about a possible role in atopic disease. As atopic diseases are considered to be the result of a disturbance in the balance between T helper cells type 2 and regulatory T cells, it is of interest to know whether hsp60 acts as a bystander antigen in atopic disease. Our aim was to investigate whether hsp60 is involved in the chronicity of inflammation of atopic dermatitis (AD). We studied the expression of hsp60 in skin tissue of adults with AD by immunohistochemistry. Peripheral blood mononuclear cells (PBMC) of children with AD were cultured with hsp60 and proliferative responses, cytokine secretion, surface markers, and functional assays were compared to responses of PBMC of healthy controls (HC). Hsp60 was detected more in lesional skin of AD patients compared to nonlesional skin. Furthermore, PBMC of children with AD proliferated more strongly in response to hsp60 compared to HC. hsp60-reactive T cells of atopic children produced high levels of IFNγ and low levels of IL-10. In vitro activation with hsp60 leads to the induction of CD4 + CD25 bright T cells expressing FOXP3 in both HC as well as in atopic children. However, despite their regulatory phenotype, hsp60-induced CD4 + CD25bright CD127− FOXP3 + T cells of AD patients were incapable of suppressing effector T cells in vitro. hsp60 is recognized by proinflammatory (IFNγ high, IL-10 low) T cells in atopic patients and is more present in lesional AD skin. This suggests that hsp60-specific T cell responses contribute to local inflammation in AD.

show abstract

The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat‐shock protein 60 capable of producing the regulatory cytokine interleukin‐10

Abstract: Objective. To test the hypothesis that T cell reactivity to self heat-shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism.Methods. Using peripheral blood-derived mononuclear cells (

Cited by 120 publications

References 43 publications

PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis

PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis

Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis

Contact Info

Product

Resources

About