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Effect of Schlafen 2 on natural killer and T cell development from common T/natural killer progenitors.

Abstract

Natural Killer (NK) cells are thought to develop from common lymphoid progenitors in the bone marrow. Even though thymus is not essential for NK cell development, T-cell/natural killer-cell (T/NK) precursors, DN1 (CD44+CD25-) and DN2 (CD44+CD25+) when cultured on an OP9 stroma, give rise to some NK1.1 cells. Genes of the Schlafen (Slfn) family are involved in hematopoietic and immune processes. The contribution of the Slfn genes in NK cell development from Double Negative (DN) cells is unknown. We transduced DN1 and DN2 progenitors prepared from C57BL/6 (B6) mouse thymus with Schlafen 1 (Slfnl) and Schlafen 2 (Slfn2) genes using Mig retroviral vector containing the Green Fluorescent Protein (GFP) gene and cultured those transduced progenitors on OP9 and OP9 stroma expressing the Notch ligand Delta-like 1 (OP9-DL 1) with appropriate cytokines to see if they affect generating NK and T-cells differently. Maturation of both NK and T cells from immature T/NK thymocytes hampered by Slfn1 and Slfn2 transduction but we got a small number of Slfn1 and Slfn2 expressing cells upon culture of transduced DN progenitors on stroma cells. There was no difference between Slfn1 expressing (GFP+) and none expressing T cells regarding CD3 expression but all mature NK cells were from Slfn1 negative population. Slfn2 completely blocked maturation of T cells but there was no difference between Slfn2 expressing and none expressing NK cells. Based on our findings both Slfn1 and Slfn2 interfere with maturation of DN2 progenitors but T cell development is more sensitive to Slfn2 expression than NK cell.

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  • Authors

    Ahmadi S, Veinotte LL

    Institution

    Kurdistan Centre for Cell and Molecular Research, Kurdistan University of Medical Sciences, Sanandaj, Kurdistan, Iran.

    Source

    Pakistan journal of biological sciences: PJBS 14:22 2011 Nov 15 pg 1002-10

    MeSH

    Animals
    Cell Cycle Proteins
    Cell Differentiation
    Cell Line
    Cytokines
    Fibroblasts
    Hematopoietic Stem Cells
    Killer Cells, Natural
    Lymphoid Progenitor Cells
    Mice
    Mice, Inbred C57BL
    NIH 3T3 Cells
    Stromal Cells
    T-Lymphocytes
    Thymocytes

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22514877