Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: Involvement of phosphatidylinositol 3-kinase and nuclear factor ?B pathways in tumor necrosis factor ? production in rheumatoid arthritis

Brennan, Fionula M.; Hayes, Amanda L.; Ciesielski, Cathleen J.; Green, Patricia; Foxwell, Brian M. J.; Feldmann, Marc

doi:10.1002/1529-0131(200201)46:1<31::aid-art10029>3.0.co;2-5

Cited by 144 publications

(136 citation statements)

References 36 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Under specific circumstances, such as tissue trauma or infection, this could result in inappropriate autoreactivity. Consistent with this hypothesis, synovial T cells in RA patients have recently been likened to cytokine-activated T cells, 42 and the latter have been shown to elicit a proinflammatory response from monocytes. 43 Additionally, clonal expansion of unusual CD4 ϩ T-cell subsets lacking CD28 and CD7 expression or expressing CD57 have been reported in RA.…”

Section: Discussionmentioning

confidence: 71%

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Ponchel

Morgan

Bingham

et al. 2002

Blood

147

137

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 71%

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Ponchel

Morgan

Bingham

et al. 2002

Blood

147

137

View full text Add to dashboard Cite

“…Whatever the stage of the responding T cells, a balance between maintenance of memory and a potentially pathological effect of cytokine-activated cells must be struck. While cytokine-activated T cells may normally be transient, and appear less able than antigen-activated T cells to mediate downstream effects on other cells, they nevertheless could contribute to ongoing inflammation in autoimmune disease [26,27].…”

Section: Discussionmentioning

confidence: 99%

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

et al. 2010

View full text Add to dashboard Cite

Antigen-specific CD4 1 T cells are central to natural and vaccine-induced immunity. An ongoing antigen-specific T-cell response can, however, influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated whether boosting memory CD4 1 T cells against TT in vivo would influence injected CD4 1 TCR transgenic T cells (OT-II) specific for an unrelated OVA peptide. If OT-II cells were pre-activated with OVA peptide in vitro, these cells showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naive mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This crosstalk between a stimulated CD4 1 memory T-cell response and CD4 1 T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens.

show abstract

“…Resting T cells (Trest) had been freshly isolated. Cytokine-activated T cells (Tck) were stimulated by a mix of 25 ng/ml TNF-␣, 100 ng/ml IL-6, and 25 ng/ml IL-2 for 8 days (25). T cells were activated with superantigen staphylococcal enterotoxin A (10 ng/ml, Tsea) by coculture with IFN-␥-stimulated FLS (2).…”

Section: T Cell Generationmentioning

confidence: 99%

“…Tsea were T cells that had been stimulated through their TCR by superantigen presented by FLS. Tck were activated with a cytokine mix (and not by the TCR), consisting of IL-6, TNF-␣, and IL-2, and represent a population that share characteristics similar to T cells isolated from RA synovial fluid (25). Trest were T cells that were purified from peripheral blood and not otherwise stimulated.…”

Section: B7-h3 Localizes To the Contact Point Between Fls And T Cellsmentioning

confidence: 99%

Interactions of T Cells with Fibroblast-Like Synoviocytes: Role of the B7 Family Costimulatory Ligand B7-H3

Tran

Thacker

Louie

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Fibroblast-like synoviocytes (FLS) and T cells can activate each other in vitro, and in vivo interactions between these cells may be important in rheumatoid arthritis (RA), yet FLS lack significant expression of CD28 ligands. We sought to identify molecules homologous to CD28 ligands that are strongly expressed by FLS, and documented strong B7-H3 expression on FLS and by fibroblasts of other tissues, which was unaffected by a variety of cytokines. Western blot analysis of FLS lysates showed predominant expression of the larger, four Ig-like domain isoform of B7-H3. Immunohistological sections of RA synovial tissue showed strong staining for B7-H3 on FLS. Cells expressing B7-H3 were distinct from but in close proximity to cells that expressed CD45, CD20, and CD3. Confocal microscopy of FLS and T cell cocultures showed localization of B7-H3 in the region of the T cell-FLS contact point, but distinct from the localization of T cell CD11a/CD18 (LFA-1) and FLS CD54 (ICAM-1). Reduction of B7-H3 expression on FLS by RNA interference affected interactions of FLS with resting T cells or cytokine-activated T cells. Resting T cells showed increased production of TNF-α, IFN-γ, and IL-2, whereas cytokine-activated T cells showed reduced cytokine production relative to control. However, cytokine production by T cells activated through their TCR was not notably altered by knock down of B7-H3. These observations suggest that B7-H3 may be important for the interactions between FLS and T cells in RA, as well as other diseases, and the outcome of such interactions depends on the activation state of the T cell.

show abstract

Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: Involvement of phosphatidylinositol 3-kinase and nuclear factor ?B pathways in tumor necrosis factor ? production in rheumatoid arthritis

Cited by 144 publications

References 36 publications

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Interactions of T Cells with Fibroblast-Like Synoviocytes: Role of the B7 Family Costimulatory Ligand B7-H3

Contact Info

Product

Resources

About

Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: Involvement of phosphatidylinositol 3-kinase and nuclear factor ?B pathways in tumor necrosis factor ? production in rheumatoid arthritis

Cited by 144 publications

References 36 publications

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid

Interactions of T Cells with Fibroblast-Like Synoviocytes: Role of the B7 Family Costimulatory Ligand B7-H3

Contact Info

Product

Resources

About

Bystander stimulation of activated CD4⁺ T cells of unrelated specificity following a booster vaccination with tetanus toxoid