Cyclosporin A inhibits CD40 ligand expression in T lymphocytes.

Fuleihan, Ramsay; Ramesh, Narayanaswamy; Horner, Anthony A.; Ahern, Deborah; Belshaw, Peter J.; Alberg, David G.; Stamenkovic, Ivan; Harmon, William; Geha, Raif S.

doi:10.1172/jci117089

Cited by 132 publications

(101 citation statements)

References 51 publications

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“…15 X-linked hyper IgM (X-HIM) is a primary immune deficiency disease that results from defects in the gene for CD40 ligand. 16 CD40 ligand is a 39 kDa glycoprotein expressed transiently on the surface of activated CD4 + T cells 17 and delivers contact-dependent help to B cells and monocytes. 18 Affected patients suffer from recurrent infections including opportunistic infections, recurrent episodes of neutropenia and autoimmune disease, and have an increased likelihood of developing cancer.…”

Section: Introductionmentioning

confidence: 99%

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Zhang

Fuleihan

1999

Gene Ther

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We examined the ability of recombinant adeno-associated no detectable constitutive expression of luciferase and that virus (rAAV) to transfer regulated gene expression into T luciferase gene expression remained inducible for at least cell lines. An AAV-based vector containing the neomycin 180 days. Luciferase expression was activated by PMA resistance gene and expressing the firefly luciferase (luc) and ionomycin and by anti-CD3 antibodies and was gene under the regulatory control of the interleukin 2 proinhibited by cyclosporin A. Examination of G418-resistant moter (pAAV-luc) was generated and adenovirus-free clones showed that rAAV-luc had integrated into the host rAAV (rAAV-luc) was produced from this vector. Transfecchromosomes but that some of the clones lost some of tion of pAAV-luc into the human T cell line Jurkat resulted the transferred DNA or lost expression from the transferred in luciferase expression while infection of Jurkat T cells DNA. These results indicate that rAAV can transfer and with rAAV-luc resulted in significant luciferase expression integrate regulated gene expression into T cell lines but only after selection for neomycin-resistant cells. Long-term that the transferred genetic material may be lost or its growth of transduced Jurkat T cells showed that there was expression may be silenced over time.

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Section: Introductionmentioning

confidence: 99%

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Zhang

Fuleihan

1999

Gene Ther

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“…We, and others, have previously showed that peripheral blood mononuclear cells (PBMCs) isolated from OLT recipients on conventional immunosuppression (tacrolimus, prednisolone) have impaired CD154 gene and protein expression after in vitro stimulation (12,28,29). This is thought to be the result of CD154 expression being partially dependant on the dephosphorylation of nuclear factor of activated T cells (NF-AT), the target of calcineurin antagonists, as the CD154 promoter has been found to contain an NF-AT binding site (28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…This is thought to be the result of CD154 expression being partially dependant on the dephosphorylation of nuclear factor of activated T cells (NF-AT), the target of calcineurin antagonists, as the CD154 promoter has been found to contain an NF-AT binding site (28)(29)(30)(31). However, an increased intragraft expression of costimulatory transcripts in patients on calcineurin-based immunosuppression has been reported by some investigators (7).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Bartlett¹,

McCall²,

Ameratunga³

et al. 2003

American Journal of Transplantation

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CD40-CD154 and/or CD28-CD80/86 costimulatory blockade induces long-term allograft survival in numerous animal models. Studies examining the expression of costimulatory molecules during acute cellular rejection (ACR) have been limited to renal and cardiac allografts.The aim of this study was to describe the relationship between intragraft costimulatory molecule expression in OLT recipients and ACR. Forty-five liver biopsies were obtained at reperfusion and day 7. Gene and protein expression of CD80, CD86 and CD154 were analyzed by RT-PCR and immunohistochemistry. CD154 protein expression was present in 13 of 18 patients with a RAI score of 4, but in only two of 14 patients with a RAI score of <4. There was a strong association between the RAI score and the presence of CD80 and CD154 immunoreactivity. CD86 protein expression did not correlate with the severity of ACR. In reperfusion biopsies CD154, but not CD80 or CD86, protein expression correlated with the total ischaemic time. There was no association between expression of costimulatory molecule genes and ACR.In conclusion, we have demonstrated an association between CD154 and CD80 protein expression and ACR in orthotopic liver allografts.

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“…Cyclosporine (CsA), a powerful inhibitor of the calcineurin pathway, has been previously shown to eliminate CD40L expression on normal T cells. More specifically, only 4% of T cells from healthy subjects express CD40L upon activation, in the presence of CsA at concentrations of 100 ng/ml, compared to 62% in the absence of CsA (18).…”

Section: Regulation Of Cd40l Expressionmentioning

confidence: 99%

Targeting CD40L: a Promising Therapeutic Approach

Daoussis

Andonopoulos

Liossis

2004

Clin Vaccine Immunol

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Cyclosporin A inhibits CD40 ligand expression in T lymphocytes.

Abstract: The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent

Cited by 132 publications

References 51 publications

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Transfer of activation-dependent gene expression into T cell lines by recombinant adeno-associated virus

Analysis of Intragraft Gene and Protein Expression of the Costimulatory Molecules, CD80, CD86 and CD154, in Orthotopic Liver Transplant Recipients

Targeting CD40L: a Promising Therapeutic Approach

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