scholarly journals Suppression of T cell responses by chondromodulin I, a cartilage-derived angiogenesis inhibitory factor: Therapeutic potential in rheumatoid arthritis

2004 ◽  
Vol 50 (3) ◽  
pp. 828-839 ◽  
Author(s):  
Keigo Setoguchi ◽  
Yoshikata Misaki ◽  
Kimito Kawahata ◽  
Kota Shimada ◽  
Takuo Juji ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Therapeutic Potential ◽  
T Cell Responses ◽  
Inhibitory Factor ◽  
Cell Responses

Emergence of proinflammatory autoreactive T-cell responses in preclinical rheumatoid arthritis

The Lancet ◽  
2014 ◽  
Vol 383 ◽  
pp. S22 ◽  
Author(s):  
Aamir Aslam ◽  
Jackie Nam ◽  
Laura Hunt ◽  
Chadi Rakieh ◽  
Ann Morgan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Autoreactive T Cell

T cell responses to citrullinated self-peptides in patients with rheumatoid arthritis

2013 ◽  
Vol 33 (9) ◽  
pp. 2359-2363 ◽  
Author(s):  
Amita Aggarwal ◽  
Rajni Srivastava ◽  
Suraksha Agrawal
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Self Peptides

scholarly journals O1 T cell responses to citrullinated self-peptides in patients with rheumatoid arthritis

2009 ◽  
Vol 4 (3) ◽  
pp. S3
Author(s):  
Amita Aggarwal ◽  
Rajni Srivastava ◽  
Ramnath Misra ◽  
S Agrawal
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Self Peptides

Lactobacillus helveticus suppresses experimental rheumatoid arthritis by reducing inflammatory T cell responses

2015 ◽  
Vol 13 ◽  
pp. 350-362 ◽  
Author(s):  
Jung-Eun Kim ◽  
Chang Suk Chae ◽  
Gi-Cheon Kim ◽  
Won Hwang ◽  
Ji-sun Hwang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Responses ◽  
Lactobacillus Helveticus ◽  
Cell Responses

T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles

1999 ◽  
Vol 42 (7) ◽  
pp. 1497-1507 ◽  
Author(s):  
Andrew P. Cope ◽  
Salil D. Patel ◽  
Frances Hall ◽  
Mauro Congia ◽  
Henk A. J. M. Hubers ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Responses ◽  
Human Cartilage ◽  
Cell Responses

Loss of balance between protective and pro-inflammatory synovial tissue T-cell polyfunctionality predates clinical onset of rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2021-220458
Author(s):  
Achilleas Floudas ◽  
Nuno Neto ◽  
Carl Orr ◽  
Mary Canavan ◽  
Phil Gallagher ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Synovial Tissue ◽  
Flow Cytometric Analysis ◽  
T Cell Responses ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Pathway Enrichment Analysis ◽  
Cell Responses

ObjectivesThis study investigates pathogenic and protective polyfunctional T-cell responses in patient with rheumatoid arthritis (RA), individuals at risk (IAR) and healthy control (HC) synovial-tissue biopsies and identifies the presence of a novel population of pathogenic polyfunctional T-cells that are enriched in the RA joint prior to the development of clinical inflammation.MethodsPathway enrichment analysis of previously obtained RNAseq data of synovial biopsies from RA (n=118), IAR (n=20) and HC (n=44) was performed. Single-cell synovial tissue suspensions from RA (n=10), IAR (n=7) and HC (n=7) and paired peripheral blood mononuclear cells (PBMC) were stimulated in vitro and polyfunctional synovial T-cell subsets examined by flow cytometric analysis, simplified presentation of incredibly complex evaluations (SPICE) and FlowSom clustering. Flow-imaging was utilised to confirm specific T-cell cluster identification. Fluorescent lifetime imaging microscopy (FLIM) was used to visualise metabolic status of sorted T-cell populations.ResultsIncreased plasticity of Tfh cells and CD4 T-cell polyfunctionality with enriched memory Treg cell responses was demonstrated in RA patient synovial tissue. Synovial-tissue RNAseq analysis reveals that enrichment in T-cell activation and differentiation pathways pre-dates the onset of RA. Switch from potentially protective IL-4 and granulocyte macrophage colony stimulating factor (GMCSF) dominated polyfunctional CD4 T-cell responses towards pathogenic polyfunctionality is evident in patient with IAR and RA synovial tissue. Cluster analysis reveals the accumulation of highly polyfunctional CD4+ CD8dim T-cells in IAR and RA but not HC synovial tissue. CD4+ CD8dim T-cells show increased utilisation of oxidative phosphorylation, a characteristic of metabolically primed memory T-cells. Frequency of synovial CD4+ CD8dim T-cells correlates with RA disease activity.ConclusionSwitch from potentially protective to pathogenic T-cell polyfunctionality pre-dates the onset of clinical inflammation and constitutes an opportunity for therapeutic intervention in RA.

Prolonging the Incubation of Monocytes with GM-CSF and IL-4 for More Than 3 Days during the Generation of Dendritic Cells (DCS) In Vitro Markedly Diminishes IL-12 and Increases IL-10 Production When DCS Are Subsequently Matured.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3653-3653
Author(s):  
Abdul Tawab ◽  
Yong Fan ◽  
Thao Mai ◽  
Elizabeth J. Read ◽  
Roger J. Kurlander
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Therapeutic Potential ◽  
T Cell Responses ◽  
Cell Polarization ◽  
Poly I:C ◽  
Ccr7 Expression ◽  
Gm Csf ◽  
Cell Responses

Abstract Dendritic cells (DCs) are potent antigen presenting cells with therapeutic potential in stimulating host T cell responses against cancer and microbial pathogens. For this purpose, monocytes can be transformed into DCs by incubation with GM-CSF and IL-4. The resulting immature DCs are usually “matured” before use to enhance the expression of MHC products (for antigen presentation), CD83 (for optimal T response costimulation), chemokine receptor 7 (CCR7) (for migration to T cell rich areas within lymph nodes), and IL-12 (for induction of type 1 immune T cell responses). There is still no consensus on the best protocol for generating clinical grade DCs. In practice, monocytes are differentiated using GM-CSF/IL-4 for up to a week and then matured using a wide variety of agents for another 8 to 48 h. The current studies address how the duration of the differentiation and maturation steps affect DC expression of CD83, CCR7, and IL12. DCs were grown in RPMI 1640 with 10% human serum containing 2000 units/ml each of IL-4 and GM-CSF for 2 to 7 days with periodic refeeding to promote differentiation. Cells were then matured using 100 ng/ml of LPS plus 1000 units/ml of γ-IFN. DCs exposed to LPS/γ-IFN rapidly upregulated CD83, CCR7, and IL-12 expression. CD83 levels were near maximal within 8 h, while CCR7 expression and IL-12 expression reached peak levels within 18 h. Variations in the duration of DC incubation with GM-CSF/IL-4 had little impact on CD83 and CCR7 expression, but markedly affected cytokine secretion. IL-12 production by DCs during maturation and after restimulation with CD40L dropped progressively as the length of GM-CSF/IL-4 incubation was prolonged. In matched studies using 4 separate donors, DCs incubated with CSF/IL-4 for 3 days produced a log mean of 23,400 pg/ml of IL-12 during maturation and 17,900 pg/ml after CD40L restimulation. After incubation with GM-CSF/IL-4 for 7 days, DCs produced 1,500 pg/ml of IL-12 on direct stimulation and only 100 pg/ml on restimulation. IL-10 production showed the opposite pattern. DCs incubated for 7 days with GM-CSF/IL-4 produced a log mean of 370 pg/ml of IL-10 on restimulation compared to 20 pg/ml by matched cells incubated for only 3 days. These differences in IL-12 and IL-10 production were all significant in a paired t-test at p<0.01. This pattern was not unique to cells matured using LPS/γ-IFN. Similarly designed studies comparing IL-12 and IL-10 production by DCs matured using two other common maturation mixtures, poly-(I:C) (20 μg/ml) plus γ-IFN and CD40L (1 μg/ml) plus γ-IFN demonstrated the same pattern of reduced IL-12 production and increased IL-10 production when cells were cultured for extended periods. The results suggest it may be advantageous to avoid incubation of monocytes in GM-CSF/IL-4 beyond 3 days when generating DCs intended to promote type 1 T cell responses. Indeed, if endogenous DCs and DCs generated ex vivo regulate IL-12 production similarly, DC age could be a significant factor determining how DCs shape type 1 and 2 T cell polarization in vivo.

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