G-CSF-treated donor CD4+ T cells attenuate acute GVHD through a reduction in Th17 cell differentiation

Joo, Young-Don; Lee, Won-Sik; Won, Hae-Jeong; Lee, Soung-Min; Kim, Hye Ran; Park, Ji Kyoung; Park, Sae-Gwang; Choi, Il‐Whan; Choi, Inhak; Seo, Su‐Kil

doi:10.1016/j.cyto.2012.06.289

Cited by 8 publications

(5 citation statements)

References 35 publications

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“…In our analysis, GATA3 levels in T cells did not change significantly in CD3+ T cells following G-CSF mobilization, although our genotype study did not include an analysis that was specific for the CD4+ T cell subset. Recent data suggest reductions in Th17 cells may be partially responsible for the avoidance of acute GVHD in G-CSF mobilized allografts (38). However, using a Luminex array analysis, we observed no changes in serum IL-17 levels following G-CSF mobilization.…”

Section: Discussionmentioning

confidence: 99%

Differences in the Phenotype, Cytokine Gene Expression Profiles, and In Vivo Alloreactivity of T Cells Mobilized with Plerixafor Compared with G-CSF

Lundqvist

Smith

Takahashi

et al. 2013

The Journal of Immunology

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Plerixafor (Mozobil®) is a CXCR4 antagonist that rapidly mobilizes CD34+ cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T-cells, the effects of plerixafor mobilization on T-cells have not been well characterized. In this study, we show that alterations in the T-cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur following mobilization with plerixafor. Compared to non-mobilized T-cells, plerixafor-mobilized T-cells had similar phenotype, mixed lymphocyte reactivity, FoxP3 gene expression levels in CD4+ T-cells, and did not undergo a change in expression levels of 84 genes associated with Th1/Th2/Th3 pathways. In contrast to plerixafor, G-CSF mobilization decreased CD62L expression on both CD4 and CD8+ T-cells and altered expression levels of 16 cytokine-associated genes in CD3+ T-cells. To assess the clinical relevance of these findings, we explored a murine model of GVHD in which transplant recipients received plerixafor or G-CSF mobilized allograft from MHC-matched, minor histocompatibility mismatched donors; recipients of plerixafor mobilized PBSC had a significantly higher incidence of skin GVHD compared to mice receiving G-CSF mobilized transplants (100% vs. 50% respectively, p=0.02). These preclinical data show plerixafor, in contrast to G-CSF, does not alter the phenotype and cytokine polarization of T-cells, which raises the possibility that T-cell mediated immune sequelae of allogeneic transplantation in humans may differ when donor allografts are mobilized with plerixafor compared to G-CSF.

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Section: Discussionmentioning

confidence: 99%

Differences in the Phenotype, Cytokine Gene Expression Profiles, and In Vivo Alloreactivity of T Cells Mobilized with Plerixafor Compared with G-CSF

Lundqvist

Smith

Takahashi

et al. 2013

The Journal of Immunology

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“…Joo et al . report that expression of SOCS3 in G‐CSF‐treated donor CD4 + T cells attenuates acute GVHD by a reduction in Th17 cell differentiation. More recently, Roman et al .…”

Section: Discussionmentioning

confidence: 94%

“…It has been reported that the expression or a deficiency of SOCS3 affects the development of acute GVHD and pancreatic islets allograft rejection . More recently, SOCS3, expressed in recipients after allogeneic HSCT was also associated with the development of GVHD .…”

Section: Discussionmentioning

confidence: 99%

Suppressor of cytokine signaling 3 (SOCS3) gene transfer prolongs the survival of the murine cardiac allograft by attenuating interleukin-17-producing alloreactive T-cell responses

Zheng

Gong

et al. 2014

J Gene Med

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“…Moreover, findings originating from the same study revealed that levels of mRNA encoding the Th17-specific transcription factor RORγt were significantly decreased in T cells isolated from G-CSF-mobilized peripheral blood stem cell harvests [35]. Further, also from a mechanistic perspective, another study demonstrated that rG-CSF directly modulated CD4+ T cell responses via upregulation of expression of the protein suppressor of cytokine signaling-3 (SOCS3), resulting in attenuation of Th17-mediated aGVHD [36]. In contrast, however, others have reported that utilization of rG-CSF to mobilize stem cells is associated with increased numbers of Th17 cells in the circulation that may exacerbate GVHD [37,38].…”

Section: T Helper 17 Cellsmentioning

confidence: 90%

Contrasting Immunopathogenic and Therapeutic Roles of Granulocyte Colony-Stimulating Factor in Cancer

2020

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Tumor cells are particularly adept at exploiting the immunosuppressive potential of neutrophils as a strategy to achieve uncontrolled proliferation and spread. Recruitment of neutrophils, particularly those of an immature phenotype, known as granulocytic myeloid-derived suppressor cells, is achieved via the production of tumor-derived granulocyte colony-stimulating factor (G-CSF) and neutrophil-selective chemokines. This is not the only mechanism by which G-CSF contributes to tumor-mediated immunosuppression. In this context, the G-CSF receptor is expressed on various cells of the adaptive and innate immune systems and is associated with induction of T cell polarization towards the Th2 and regulatory T cell (Treg) phenotypes. In contrast to the potentially adverse effects of sustained, endogenous production of G-CSF by tumor cells, stringently controlled prophylactic administration of recombinant (r) G-CSF is now a widely practiced strategy in medical oncology to prevent, and in some cases treat, chemotherapy-induced severe neutropenia. Following an overview of the synthesis, structure and function of G-CSF and its receptor, the remainder of this review is focused on: (i) effects of G-CSF on the cells of the adaptive and innate immune systems; (ii) mechanisms by which this cytokine promotes tumor progression and invasion; and (iii) current clinical applications and potential risks of the use of rG-CSF in medical oncology.

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G-CSF-treated donor CD4+ T cells attenuate acute GVHD through a reduction in Th17 cell differentiation

Cited by 8 publications

References 35 publications

Differences in the Phenotype, Cytokine Gene Expression Profiles, and In Vivo Alloreactivity of T Cells Mobilized with Plerixafor Compared with G-CSF

Differences in the Phenotype, Cytokine Gene Expression Profiles, and In Vivo Alloreactivity of T Cells Mobilized with Plerixafor Compared with G-CSF

Suppressor of cytokine signaling 3 (SOCS3) gene transfer prolongs the survival of the murine cardiac allograft by attenuating interleukin-17-producing alloreactive T-cell responses

Contrasting Immunopathogenic and Therapeutic Roles of Granulocyte Colony-Stimulating Factor in Cancer

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