Hematopoietic progenitor cell regulation by CD4+CD25+ T cells

Urbieta, Maitee; Barão, Isabel; Jones, Mark S.; Jurecic, Roland; Panoskaltsis‐Mortari, Angela; Blazar, Bruce R.; Murphy, William J.; Levy, Robert B.

doi:10.1182/blood-2009-04-218826

Cited by 37 publications

(36 citation statements)

References 55 publications

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“…205,206 Depletion experiments and co-transfer of BM with regulatory T cells indicated that these cells suppress colony formation and myeloid differentiation of HSCs. 207 Moreover, FoxP3 + regulatory T cells colocalize with HSCs in the endosteal surface in the calvarial and trabecular BM, and this colocalization is lost after depletion of regulatory T cells. 208 However, whether this interaction is biologically relevant to the homeostatic HSC maintenance is still unclear.…”

Section: Heterogeneity Of Cells Of the Nichementioning

confidence: 97%

Niche heterogeneity in the bone marrow

Birbrair

Frenette

2016

Annals of the New York Academy of Sciences

244

185

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In adult mammals, hematopoietic stem cells (HSCs) are defined by their abilities to self-renew and to differentiate to form all blood cell lineages. These rare multipotent cells occupy specific locations in the bone marrow microenvironment. The specific microenvironment regulating HSCs, commonly referred to as the niche, comprises multiple cell types whose exact contributions are under active investigation. Understanding cellular cross talk involving HSCs in the bone marrow microenvironment is of fundamental importance for harnessing therapies against benign and malignant blood diseases. In this review, we summarize and evaluate recent advances in our understanding of niche heterogeneity and its influence on HSC function.

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Section: Heterogeneity Of Cells Of the Nichementioning

confidence: 97%

Niche heterogeneity in the bone marrow

Birbrair

Frenette

2016

Annals of the New York Academy of Sciences

244

185

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“…Unlike the regulation of myeloid lineages demonstrated previously [24], the mechanism underlying the effect of Treg cells seems not to include their direct action on progenitors because they did not directly alter the developmental fate of LSK cells cultured under B-cell-polarizing conditions. Rather, Treg cells exerted their effects by constraining the activity of Teff cells.…”

Section: Discussionmentioning

confidence: 89%

“…This discrepancy may stem from differences in the environmental factors the mice were exposed to, e.g. the type of commensal microbiota, that may interfere with processes genetically imprinted by the Foxp3 mutation.Unlike the regulation of myeloid lineages demonstrated previously [24], the mechanism underlying the effect of Treg cells seems not to include their direct action on progenitors because they did not directly alter the developmental fate of LSK cells cultured under B-cell-polarizing conditions. Rather, Treg cells exerted their effects by constraining the activity of Teff cells.…”

mentioning

confidence: 89%

Foxp3⁺ regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow

et al. 2014

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Foxp3 + Treg cells are crucial for maintaining T-cell homeostasis, but their role in B-cell homeostasis remains unclear. Here, we found that Foxp3 mutant scurfy mice had fewer B-lineage cells and progenitors, including common lymphoid progenitors and lymphoidprimed multipotent progenitors, but higher myeloid-lineage cell numbers in BM compared with WT littermates. Homeostasis within the HSC compartment was also compromised with apparent expansion of long-and short-term HSCs. This abnormality was due to the lack of Treg cells, but not to the Treg-cell extrinsic functions of Foxp3 or cellautonomous defects. Among cytokines enriched in the BM of scurfy mice, IFN-γ affected only B lymphopoiesis, but GM-CSF, TNF, and IL-6 collectively promoted granulopoiesis at the expense of B lymphopoiesis. Neutralization of these three cytokines reversed the hematopoietic defects on early B-cell progenitors in scurfy mice. Treg cells ensured B lymphopoiesis by reducing the production of these cytokines by effector T cells, but not by directly affecting B lymphopoiesis. These results suggest that Treg cells occupy an important niche in the BM to protect B-lineage progenitor cells from excessive exposure to a lymphopoiesis-regulating milieu.Keywords: B lymphopoiesis r Foxp3 r Granulopoietins r Hematopoiesis r Regulatory T cells Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction CD4 + Foxp3 + Treg cells are essential for maintaining immune homeostasis, as evidenced by the severe autoimmune lymphoproliferative disease observed in Treg-cell-deficient mice and humans [1,2]. Treg cells were initially identified in the secondary lymphoid tissues where they suppress the initial priming and Correspondence: Prof. Jeehee Youn e-mail: jhyoun@hanyang.ac.kr effector differentiation of autoreactive T cells [3]. They function by directly suppressing T cells and/or interacting with DCs to limit their ability to prime T cells effectively [4,5]. In addition to their constitutive presence in secondary lymphoid tissues, Treg cells have been found in several nonlymphoid sites, such as mucosal tissue, skin, liver, and lung, during inflammation as well as in steady-state conditions [6][7][8][9][10]. These Treg cells appear to regulate * These authors contributed equally to this work. * * These senior authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 168Sunghoon Kim et al. Eur. J. Immunol. 2015. 45: 167-179 tissue-tropic autoimmunity and inflammation, and alter pathogen clearance during peripheral infection. A diverse array of adhesion molecules and chemokine receptors that are expressed on Treg cells seem to license them to migrate to peripheral tissues. A fraction of Treg cells have been shown to express the BM homing receptor CXCR4 [11], suggesting the existence of a niche for Treg cells in the BM. Indeed, there are studies showing that healthy human BM contains a substantial number of Treg cells that traffic via CXC...

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“…45,46 Briefly, T cells were removed by incubation with anti-CD90.2 (HO134), anti-CD4 (RL174), and anti-CD8 (H022) ascites (1:5) with 12% (v/v) Low-Tox M rabbit complement (Cedarlane Labs) at a final concentration of 25.0 3 10 6 cells/mL on ice for 15 minutes, followed by 37°C incubation for 30 minutes. B6 mice were conditioned with 9.5-Gy total body irradiation.…”

Section: Bm Transplantationmentioning

confidence: 99%

“…Polyclonal CD4 1 and CD8 1 T cells were enriched ($75%) following B-cell depletion ($90%) from the spleen and LNs of donor mice using plate-bound goat anti-mouse IgG/M as previously described (Millipore). 45,46 Polyclonal CD4 1 ($88%) and CD8 1 ($90%) T cells were purified by negative selection following B-cell depletion.…”

Section: Cd8mentioning

confidence: 99%