Polarization of T Lymphocytes Is Regulated by Mesenchymal Stem Cells in NZBWF1 and BALB/c Mice

Abstract

Mesenchymal stem cells (MSCs) have been shown to suppress proliferation and activation of T lymphocytes in vivo and in vitro although the molecular mechanism of the immunosuppressive effect is not completely understood. To investigate the immunoregulatory effects of mice bone marrow mesenchymal stem cells on T lymphocyte, MSCs from NZBWF1 and BALB/c mice were isolated and expanded from bone marrow, and identified with cell morphology and the surface phenotypes. CD3 + T lymphocytes isolated by nylon wool columns were co-cultured with PMA with or without the two strains of MSCs. Then T cell apoptosis and intercellular cytokines of T cell were assessed by flow cytometry. Quantification of transcription factors T-box (T-bet) and GATA-binding protein 3 (GATA-3) expressed in T cells was detected by RT-PCR and western blot. Our results showed that there was a decrease of CD3 + T cell apoptosis when NW MSCs or Bc MSCs were added, and an increase of Th2 subset by NW MSCs and Th1 subset by Bc MSCs were observed by co-culturing MSCs with T lymphocytes. It is suggested that, by favoring Th1-cell development and inhibitory Th2-cell development, normal MSCs might interfere with the SLE development, and that marrow-derived NW MSCs had defective immunoregulatory function when compared with MSCs from healthy mouse strains.

Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells

“…Moreover, due to their multipotency, MSC are a very attractive choice for clinical applications in several immune disorders, such as arthritis, encephalomyelitis, systemic lupus erythematosus, and in regenerative diseases, including diabetes and skin grafting [ 8 , 10 , 13 , 16 , 19 ]. Their low immunogenicity, immunomodulatory capacity and ability to differentiate into cells that regenerate damaged tissues, had already allowed the use of MSCs in clinical trials for cellular and gene therapy [ 10 , 13 , 14 , 20 - 22 ]. MSCs are able to inhibit the proliferation and function of T, B and natural killer (NK) cells, the cytolytic effects of antigen-primed cytotoxic T cells (CTL) by the induction of regulatory T cells (Treg) [ 14 , 16 , 20 , 22 ].…”

“…Their low immunogenicity, immunomodulatory capacity and ability to differentiate into cells that regenerate damaged tissues, had already allowed the use of MSCs in clinical trials for cellular and gene therapy [ 10 , 13 , 14 , 20 - 22 ]. MSCs are able to inhibit the proliferation and function of T, B and natural killer (NK) cells, the cytolytic effects of antigen-primed cytotoxic T cells (CTL) by the induction of regulatory T cells (Treg) [ 14 , 16 , 20 , 22 ]. The immune modulation by MSCs seems to be mediated by secretion of soluble factors, creating an immunosuppressive microenvironment.…”