Immune cell signaling aberrations in human lupus

Liossis, Stamatis–Nick C.; Sfikakis, Petros P.; Tsokos, George C.

doi:10.1007/bf02786511

Cited by 21 publications

(13 citation statements)

References 70 publications

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“…Sloan-Lancaster et al reported that T cell anergy correlates with decreased levels of the p21 and p23 forms of the TCR chain (55). These results are also consistent with the finding that SLE patients have more anergic T cells compared with normal donors (1,56). The fact that the decrease in the 21-and 23-kd forms of the chain in SLE patients correlates well with the decrease in the level of the detergent-soluble 16-kd form of the chain ( Figure 2C) indirectly suggests that the decrease in the phosphorylated form is not the consequence of a defective phosphorylation cascade in SLE T cells.…”

Section: Discussionsupporting

confidence: 81%

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Nambiar

Enyedy

Fisher

et al. 2002

Arthritis & Rheumatism

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Section: Discussionsupporting

confidence: 81%

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Nambiar

Enyedy

Fisher

et al. 2002

Arthritis & Rheumatism

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“…ϩ Ts in the presence of autologous macrophages because these latter cells are needed to induce CD8 ϩ T lymphocyte suppressor function (22). However, macrophage cytokine secretion likely had a poor direct effect in determining inhibition of proliferation as suggested by the fact that counteraction of inhibition was possible only when CD8…”

Section: Discussionmentioning

confidence: 99%

Impairment of CD8+ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus

Filaci

Bacilieri

Fravega

et al. 2001

The Journal of Immunology

160

146

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Alteration of T cell suppression function has been recognized in patients with systemic lupus erythematosus (SLE). Recently, CD8+ T suppressor lymphocytes (CD8+ Ts) have been generated in vitro by incubating purified CD8+ T cells with IL-2 and GM-CSF. Using this method, we generated CD8+ Ts from patients affected by SLE. No major differences were found in the CD8+ Ts phenotype between SLE patients and healthy subjects. CD8+ Ts from SLE patients with active disease did not inhibit the anti-CD3 mAb-induced proliferation of autologous PBMC, whereas CD8+ Ts from SLE patients in remission exerted an inhibitory activity comparable to normal subjects. The inhibitory effect of CD8+ Ts cells was neither mediated by cytotoxic activity nor by apoptosis induction. Two cytokines, IFN-γ and IL-6, were found to be responsible for the function of CD8+ Ts. In fact, counteraction of CD8+ Ts suppression activity was obtained by blocking IFN-γ with a specific Ab or by inhibiting CD8+ Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8+ Ts from SLE patients showed a peculiar cytokine pattern characterized by an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8+ Ts in SLE patients.

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“…3 is an autoimmune disease of unknown etiology that is characterized by multiple T cell signaling abnormalities (1). T cells from patients with SLE have been shown to have decreased levels of TCR protein and mRNA (2).…”

Section: S Ystemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

The Cyclic AMP Response Element Modulator Regulates Transcription of the TCR ζ-Chain

Tenbrock¹,

Kyttaris

Ahlmann³

et al. 2005

The Journal of Immunology

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Systemic lupus erythematosus T cells display decreased amounts of TCR ζ mRNA that results in part from limited binding of the transcriptional enhancer Elf-1 to the TCR ζ promoter. We have identified a new cis-binding site for the cAMP response element (CRE) modulator (CREM) on the TCR ζ promoter, centered on the −390 nucleotide. Transfection of T cells with an antisense CREM α plasmid reduced the binding of CREM to the TCR ζ promoter, as shown by chromatin and reporter chromatin immunoprecipitation assays, and enhanced the production of TCR ζ mRNA and protein. Mutagenesis of the −390 CRE site prevented the binding of CREM to the TCR ζ promoter. The mechanism of CREM-mediated repression appears to be chromatin dependent, because antisense CREM promotes the acetylation of histones on the TCR ζ promoter. Finally, we established an enhanced binding of CREM to the TCR ζ-chain promoter in systemic lupus erythematosus cells compared with control T cells. Our studies demonstrate that CREM α binds to the TCR ζ promoter and repress its activity.

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Immune cell signaling aberrations in human lupus

Cited by 21 publications

References 70 publications

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Abnormal expression of various molecular forms and distribution of T cell receptor ? chain in patients with systemic lupus erythematosus

Impairment of CD8+ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus

The Cyclic AMP Response Element Modulator Regulates Transcription of the TCR ζ-Chain

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