Restriction of De Novo Nucleotide Biosynthesis Interferes with Clonal Expansion and Differentiation into Effector and Memory CD8 T Cells

Quéméneur, Laurence; Beloeil, Laurent; Michallet, M; Angelov, Georgi S.; Tomkowiak, Martine; Revillard, Jean‐Pierre; Marvel, Jacqueline

doi:10.4049/jimmunol.173.8.4945

Cited by 36 publications

(31 citation statements)

References 60 publications

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“…Because of its favorable effects on Treg, sirolimus has been recently advocated as a pro-tolerogenic immunosuppressive drug (46). Moreover, MMF has been shown to prevent the differentiation of naïve T cells into memory cells and to inhibit memory cell proliferation both in vitro in human mixed lymphocyte cultures (47) and in vivo in F5 TCR transgenic mice (48). Expansion of CD4 ϩ CD25 high FOXP3 ϩ cells, however, was negligible in renal transplant patients who received the calcineurin inhibitor CsA along with MMF as maintenance therapy after Campath-1H induction.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells and T Cell Depletion

Noris¹,

Casiraghi²,

Todeschini³

et al. 2007

Journal of the American Society of Nephrology

214

170

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؉ CD25 high cells that expressed FOXP3 underwent homeostatic peripheral expansion during immune reconstitution, more intense in patients who received sirolimus than in those who were given CsA. T cells that were isolated from peripheral blood long term after transplantation were hyporesponsive to alloantigens in both groups. In sirolimus-but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated patients were anergic. Thus, lymphopenia and calcineurin-dependent signaling seem to be primary mediators of CD4 ؉ CD25 high Treg expansion in renal transplant patients. These findings will be instrumental in developing "tolerance permissive" immunosuppressive regimens in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Regulatory T Cells and T Cell Depletion

Noris¹,

Casiraghi²,

Todeschini³

et al. 2007

Journal of the American Society of Nephrology

214

170

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“…This assay was performed as described previously (25). Briefly, targets were prepared from C57BL/10 splenocytes.…”

Section: In Vivo Cytotoxic Assaymentioning

confidence: 99%

Flt3 Ligand-Generated Murine Plasmacytoid and Conventional Dendritic Cells Differ in Their Capacity to Prime Naive CD8 T Cells and to Generate Memory Cells In Vivo

Angelov

Tomkowiak

Marçais

et al. 2005

The Journal of Immunology

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Mature dendritic cells (DCs) have the capacity to induce efficient primary T cell response and effector cell differentiation. Thus, these cells are a major tool in the design of various immunotherapeutic protocols. We have tested the capacity of different subsets of matured DCs pulsed with a peptide to induce the differentiation of naive CD8 T cells into memory cells in vivo. Flt3 ligand (FL) induces the differentiation of conventional DCs (cDCs) and plasmacytoid DCs (PDCs) from murine bone marrow precursors in vitro. After maturation, both subsets become strong stimulators of Ag-specific T cell responses in vitro. However, the in vivo T cell stimulatory capacity of these DC subsets has not been studied in detail. In the present study, we demonstrate that mature FL-generated DCs induce efficient peptide-specific CD8 T cell response and memory cell differentiation in vivo. This is mainly due to the cDC subset because the PDC subset induced only a negligible primary CD8 response without detectable levels of memory CD8 T cell differentiation. Thus, in vitro FL-generated mature cDCs, but not PDCs, are potent stimulators of peptide-specific CD8 T cell responses and memory generation in vivo.

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“…These primed effector T-lymphocytes re-enter the circulation until they encounter the inflamed allograft where they can infiltrate and further amplify the graft-reactive immune response (Saiki et al, 2001). Immunosuppressive drugs in current usage target various stages of this process by inhibiting T-lymphocyte activation (Kiani et al, 2000), proliferation (Quemeneur et al, 2004), and the inflammatory processes that lead to activation of endothelial and dendritic cells (Ray and Searle, 1997;Piemonti et al, 1999). (Deng et al, 2006).…”

Section: Immunoregulatory Pathways In Transplantationmentioning

confidence: 99%

Understanding Gene Expression Patterns in Immune-Mediated Disorders

Dedrick¹

2007

Journal of Immunotoxicology

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Gene expression profiling of peripheral blood cells can provide dynamic information regarding the host response to immunemediated disorders. AlloMap R molecular expression testing from XDx monitors the expression of 20 genes in peripheral blood mononuclear cells (PBMC) to discriminate cardiac allograft recipients of 15 years or greater who are at low risk for acute cellular rejection (ACR). The AlloMap test classifier is based on the expression level of 11 genes, encoding proteins with diverse functions, which are differentially expressed in stable patients with moderate to severe ACR compared to patients without ACR. The nine other test genes are used for normalizing gene expression levels and assuring sample quality. In this work we review the development processes leading to the selection of the 11 informative genes and the derivation of the AlloMap test classifier, and discuss the relationship of peripheral blood gene expression with diverse pathways associated with ACR, including T-cell priming, platelet activation, systemic responses to allograft inflammation, and the overall state of immunosuppression.

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Restriction of De Novo Nucleotide Biosynthesis Interferes with Clonal Expansion and Differentiation into Effector and Memory CD8 T Cells

Cited by 36 publications

References 60 publications

Regulatory T Cells and T Cell Depletion

Regulatory T Cells and T Cell Depletion

Flt3 Ligand-Generated Murine Plasmacytoid and Conventional Dendritic Cells Differ in Their Capacity to Prime Naive CD8 T Cells and to Generate Memory Cells In Vivo

Understanding Gene Expression Patterns in Immune-Mediated Disorders

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