scholarly journals Killer Cell Activating Receptors Function as Costimulatory Molecules on CD4+CD28null T Cells Clonally Expanded in Rheumatoid Arthritis

2000 ◽  
Vol 165 (2) ◽  
pp. 1138-1145 ◽  
Author(s):  
Takashi Namekawa ◽  
Melissa R. Snyder ◽  
Jeng-Hsien Yen ◽  
Brenda E. Goehring ◽  
Paul J. Leibson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Killer Cell ◽  
Costimulatory Molecules ◽  
Activating Receptors

scholarly journals Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis

2001 ◽  
Vol 193 (10) ◽  
pp. 1159-1168 ◽  
Author(s):  
Jeng-Hsien Yen ◽  
Brenda E. Moore ◽  
Takako Nakajima ◽  
Dirk Scholl ◽  
Daniel J. Schaid ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Odds Ratio ◽  
Disease Risk ◽  
Association Studies ◽  
Killer Cell ◽  
Vascular Complications ◽  
Hla Class I ◽  
Class I ◽  
Rheumatoid Vasculitis

Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a cell population potentially involved in endothelial damage. CD4+CD28null T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin–like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities. To test the hypothesis that the KIR2DS2 gene is involved in the development of vasculitis, association studies were performed. The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001). Also, the distribution of human histocompatibility leukocyte antigen (HLA)-C, the putative ligand for KIRs, was significantly different in patients with rheumatoid vasculitis in comparison with the control populations. These data suggest that HLA class I–recognizing receptors and HLA class I genes are genetic risk determinants that modulate the pattern of RA expression. Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4+CD28null T cells.

scholarly journals Multiplicity and plasticity of natural killer cell signaling pathways

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2364-2372 ◽  
Author(s):  
Sabrina Chiesa ◽  
Michael Mingueneau ◽  
Nicolas Fuseri ◽  
Bernard Malissen ◽  
David H. Raulet ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Interferon Γ ◽  
Effector Functions ◽  
Activating Receptors ◽  
Cell Effector

AbstractNatural killer (NK) cells express an array of activating receptors that associate with DAP12 (KARAP), CD3ζ, and/or FcRγ ITAM (immunoreceptor tyrosine-based activation motif)–bearing signaling subunits. In T and mast cells, ITAM-dependent signals are integrated by critical scaffolding elements such as LAT (linker for activation of T cells) and NTAL (non–T-cell activation linker). Using mice that are deficient for ITAM-bearing molecules, LAT or NTAL, we show that NK cell cytotoxicity and interferon-γ secretion are initiated by ITAM-dependent and -independent as well as LAT/NTAL-dependent and -independent pathways. The role of these various signaling circuits depends on the target cell as well as on the activation status of the NK cell. The multiplicity and the plasticity of the pathways that initiate NK cell effector functions contrast with the situation in T cells and B cells and provide an explanation for the resiliency of NK cell effector functions to various pharmacologic inhibitors and genetic mutations in signaling molecules.

scholarly journals Associations of Killer Cell Immunoglobulin-Like Receptor Genes with Rheumatoid Arthritis

2012 ◽  
Vol 33 (4) ◽  
pp. 201-206 ◽  
Author(s):  
S. Ramírez-De los Santos ◽  
P. E. Sánchez-Hernández ◽  
J. F. Muñoz-Valle ◽  
C. A. Palafox-Sánchez ◽  
L. Y. Rosales-Rivera ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Healthy Subjects ◽  
Gene Frequency ◽  
Killer Cell ◽  
Chronic Inflammatory Disease ◽  
Unknown Etiology ◽  
Gene Frequencies ◽  
Western Mexico ◽  
Genotype Frequencies

Objective: Rheumatoid Arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors are expressed on the surface of natural killer cells and CD28nullT-cells, both present in synovial membrane of RA. Therefore we evaluated the associations ofKIRgenes with RA.Methods: 16KIRgenes were genotyped in 100 healthy subjects (HS) and 100 RA patients from Western Mexico using PCR-SSP. Differences inKIRgenotypes and gene frequencies were assessed using theX2test.Results: Gene frequency ofKIR2DL3was lower in RA than in HS (p= 0.0019), whereasKIR2DL2andKIR2DS2were higher in RA than HS (p= 0.0004 andp= 0.0487, respectively). In addition were identified 38 genotypes (from G1-G38) in both studied groups, and the genotype frequencies of G1, G6 and G14 showed significant differences (p= 0.0001,p= 0.0208 andp= 0.0300, respectively).Conclusions: The presence ofKIR2DL2,KIR2DS2and absence ofKIR2DL3are associated with RA. Moreover, two genotypes BX are associated with RA. These results suggest thatKIRscan be involved in RA susceptibility.

scholarly journals Engagement of NKp30 on Vδ1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4013-4016 ◽  
Author(s):  
Kelly Hudspeth ◽  
Manuela Fogli ◽  
Daniel V. Correia ◽  
Joanna Mikulak ◽  
Alessandra Roberto ◽  
...  
Keyword(s):  
T Cells ◽  
De Novo ◽  
Killer Cell ◽  
Γδ T Cells ◽  
Pathogenic Role ◽  
Activating Receptors ◽  
Antiviral Function ◽  
Cc Chemokines ◽  
Natural Cytotoxicity Receptors ◽  
Hiv 1

AbstractNatural cytotoxicity receptors (NCRs) were originally identified as specific natural killer cell activating receptors that, on binding to their endogenous ligands, trigger the killing of tumor cell targets. We recently described the differentiation of a novel subset of NCR+ Vδ1 T cells characterized by a remarkably high cytolytic potential against cancer cells. Here we demonstrate that the engagement of NKp30, one of the NCRs expressed de novo on Vδ1 T cells after stimulation, triggers the production of high levels of CCL3/MIP-1α, CCL4/ MIP-1β, and CCL5/RANTES but not of CXCL12/SDF-1. In turn, this NKp30-induced secretion of cc-chemokines is able to significantly suppress the replication of a CCR5 tropic strain of HIV-1 in CD4+/CCR5+ infected PM1 cell lines. This experimental evidence disclosing an unanticipated antiviral function of NCR+ Vδ1 T cells opens new avenues for understanding the pathogenic role and for manipulating the function of γδ T cells in HIV-1 infection.

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
pp. 1-1
Author(s):  
Jose Miguel Sempere-Ortells ◽  
Vicente Perez-Garcia ◽  
Gema Marin-Alberca ◽  
Alejandra Peris-Pertusa ◽  
Jose Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

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