Posttranscriptional Regulation of T-Cell IL-2 Production by Human Pooled Immunoglobin

Modiano, Jaime F.; Amran, David; Lack, Gideon; Bradley, Katherine; Ball, Carrie R.; Domenico, Joanne; Gelfand, Erwin W.

doi:10.1006/clin.1997.4329

Cited by 52 publications

(38 citation statements)

References 42 publications

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“…As inhibition of T-cell proliferation is one of the caveats of immunosuppression because it leads to the inhibition of the graft vs leukemia, this finding could have an impact on clinical practice. Many studies showed that IVIG inhibit T-cell proliferation or induce apoptosis 42,43,[53][54][55][56][57] whereas others failed to demonstrate any direct effect of IVIG on T-cells. 58,59 Interestingly, studies showing an inhibition of T-cell proliferation or an induction of apoptosis were performed in vitro whereas studies that failed to demonstrate any direct effect on T-cell proliferation were performed in vivo.…”

Section: Discussionmentioning

confidence: 99%

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Gregoire-Gauthier

Durrieu

Duval

et al. 2011

Bone Marrow Transplant

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The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/ccÀ (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-c and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34 þ stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.

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Section: Discussionmentioning

confidence: 99%

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Gregoire-Gauthier

Durrieu

Duval

et al. 2011

Bone Marrow Transplant

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“…RT-PCR. Messenger RNA levels also were analyzed by reverse transcription and amplification of cDNA by PCR (14). Briefly, 20 ng of total RNA were incubated with CDK4 or ␤-actin-specific primers in 50 l of a reaction buffer containing 10 mM Tris (pH 8.3), 50 mM potassium chloride, 2.5 mM magnesium chloride, 0.001% (w:v) gelatin, 200 M of each deoxynucleotide and 50 pM of oligonucleotide primer.…”

Section: Gene Expressionmentioning

confidence: 99%

“…14). Genes encoding wildtype CDK4 and kinase-inactive CDK4 (15), p16/Ink-4a (16), or p21/Waf-1 (17) were subcloned into the multiple cloning site of the pBK-RSV eukaryotic expression vector (Stratagene, La Jolla, CA).…”

Section: Transfectionsmentioning

confidence: 99%

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CDK4 Expression and Activity Are Required for Cytokine Responsiveness in T Cells

Modiano

Mayor

Ball

et al. 2000

The Journal of Immunology

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Stimulation of lymphocytes through the Ag receptor can lead to cytokine responsiveness or unresponsiveness. We examined the importance of cyclin-dependent kinase (CDK)4 to establish and maintain IL-2 responsiveness in human T cells. Our results show that a herbimycin A- and staurosporine-sensitive phase of CDK4 expression and activity preceded the acquisition of IL-2-responsiveness in mitogen-stimulated peripheral blood T cells. Intriguingly, CDK4 expression and activity were demonstrable in purified unstimulated peripheral blood T cells from ∼30% (5/16) of healthy individuals examined for this study. These T cells proliferated in response to IL-2 without additional mitogens, and both the expression and activity of CDK4 and the ability to respond to cytokines were resistant to herbimycin A and staurosporine. The pattern of CDK4 expression and response to IL-2 in this subset of individuals resembled that seen in the human IL-2-dependent Kit-225 T cell line. However, in contrast to normal T cells, Kit-225 cells were rendered unresponsive to IL-2 by stimulation through the Ag receptor. In these cells, PHA, anti-CD3, or PMA induced marked reductions of CDK4 expression and activity that paralleled IL-2 unresponsiveness, and these effects were not reversible by IL-2. Furthermore, IL-2-dependent proliferation could be similarly inhibited in Kit-225 cells by overexpression of the CDK inhibitors p16/Ink4-a or p21/Waf-1a or by overexpression of a kinase-inactive CDK4 mutant. The data indicate that CDK4 expression and activity are necessary to induce and maintain cytokine responsiveness in T cells, suggesting that CDK4 is important to link T cell signaling pathways to the machinery that controls cell cycle progression.

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“…The capability of IVIg to inhibit human T cell proliferation and cytokine production in vitro was shown to be comparable to that of calcineurin inhibitors [46,49] . It is supposed that this inhibitory effect of IVIg on T cells is at least partly caused by suppression of antigen-presenting cells, but also mediated by direct interactions [49,50] .…”

Section: Effects On T-cellsmentioning

confidence: 96%

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Kornberg¹

2015

WJH

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Posttranscriptional Regulation of T-Cell IL-2 Production by Human Pooled Immunoglobin

Cited by 52 publications

References 42 publications

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

CDK4 Expression and Activity Are Required for Cytokine Responsiveness in T Cells

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

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