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CD8 T cells drive autoimmune hematopoietic stem cell dysfunction and bone marrow failure. | LitMetric

CD8 T cells drive autoimmune hematopoietic stem cell dysfunction and bone marrow failure.

J Autoimmun

Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced, 5200 N. Lake Rd., Merced, CA 95343, USA; Health Sciences Research Institute, University of California Merced, 5200 N. Lake Rd., Merced, CA 95343, USA. Electronic address:

Published: December 2016

Bone marrow (BM) failure syndrome encompasses a group of disorders characterized by BM stem cell dysfunction, resulting in varying degrees of hypoplasia and blood pancytopenia, and in many patients is autoimmune and inflammatory in nature. The important role of T helper 1 (Th1) polarized CD4 T cells in driving BM failure has been clearly established in several models. However, animal model data demonstrating a functional role for CD8 T cells in BM dysfunction is largely lacking and our objective was to test the hypothesis that CD8 T cells play a non-redundant role in driving BM failure. Clinical evidence implicates a detrimental role for CD8 T cells in BM failure and a beneficial role for Foxp3 regulatory T cells (Tregs) in maintaining immune tolerance in the BM. We demonstrate that IL-2-deficient mice, which have a deficit in functional Tregs, develop spontaneous BM failure. Furthermore, we demonstrate a critical role for CD8 T cells in the development of BM failure, which is dependent on the cytokine, IFNγ. CD8 T cells promote hematopoietic stem cell dysfunction and depletion of myeloid lineage progenitor cells, resulting in anemia. Adoptive transfer experiments demonstrate that CD8 T cells dramatically expedite disease progression and promote CD4 T cell accumulation in the BM. Thus, BM dysregulation in IL-2-deficient mice is mediated by a Th1 and IFNγ-producing CD8 T cell (Tc1) response.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121063PMC
http://dx.doi.org/10.1016/j.jaut.2016.07.007DOI Listing

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