title: Human megakaryocyte progenitors derived from hematopoietic stem cells of normal individuals are MHC class II-expressing professional APC that enhance Th17 and Th1/Th17 responses.
abstract: Platelets, like stromal cells, present antigen only via MHC class I, but the immune potential of their progenitors has not been explored in humans. We derived CD34(+)CD117(+)CD41(+)CD151(+) megakaryocyte progenitors (MKp) in vitro from mobilized peripheral blood hematopoietic stem and progenitor cells (HSPC) of normal subjects using culture conditions akin to bone marrow niche, or organs that support extramedullary hematopoiesis. The MKp expressed MHC Class II in contrast to platelets and functioned as professional APC before they matured further. Moreover, MKp constitutively expressed mRNA encoding mediators for human Th17 expansion, including IL-1, IL-18, IL-6, TGFβ, IL-23, BAFF, and COX2. MKp also expressed high levels of type I interferon and IRF5 mRNA. In contrast to platelets, MKp augmented the expansion of Th17, Th1, and potent Th17/Th1 double-positive cells in normal PBMC and CD4 line T cells from normal subjects or lupus patients. The Th cell augmentation involved pre-committed memory cells, and was significant although modest, because only non-cognate MKp-T cell interactions could be studied, under non-polarizing conditions. Importantly, the MKp-mediated expansion was observed in the presence or absence of direct MKp-T cell contact. Furthermore, MKp augmented Th17 responses against Candida albicans, a serious opportunistic pathogen. These results indicate an immunologic role of MKp in situations associated with extramedullary hematopoiesis and mobilization of HSPC.
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Finkielsztein
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Alaina C
authors.initials: AC
authors.lastname: Schlinker
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Miller
authors.affiliation: Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: skd257@northwestern.edu.
authors.forename: Syamal K
authors.initials: SK
authors.lastname: Datta
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D000949:Histocompatibility Antigens Class II
keywords: APC; Antigen presenting cell; Hematopoiesis; Megakaryocyte progenitors; Th17 cells; Th17/Th1 cells