Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood naive, memory, and effector T cells

Abstract

IntroductionThe different distribution of T cells among activation/differentiation stages in immune disorders may condition the outcome of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in the different functional compartments of T cells is not completely elucidated.MethodsWe investigated the effect of human bone marrow MSCs on naturally occurring peripheral blood functional compartments of CD4+ and CD8+ T cells: naive, central memory, effector memory, and effector compartments. For that, mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus ionomycin were cultured in the absence/presence of MSCs. The percentage of cells expressing tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10, transforming growth factor-beta (TGF-β), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in purified CD4+ and CD8+ T cells, and phenotypic and mRNA expression changes induced by PMA + ionomycin stimulation in MSCs, were also evaluated.ResultsMSCs induced the reduction of the percentage of CD4+ and CD8+ T cells producing TNF-α, IFNγ, and IL-2 in all functional compartments, except for naive IFNγ+CD4+ T cells. This inhibitory effect differentially affected CD4+ and CD8+ T cells as well as the T-cell functional compartments; remarkably, different cytokines showed distinct patterns of inhibition regarding both the percentage of producing cells and the amount of cytokine produced. Likewise, the percentages of IL-17+, IL-17+TNF-α+, and IL-9+ within CD4+ and CD8+ T cells and of IL-6+CD4+ T cells were decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA expression in stimulated CD4+ and CD8+ T cells, whereas TGF-β was reduced in CD8+ and augmented in CD4+ T cells, with no changes for CTLA4. Finally, PMA + ionomycin stimulation did not induce significant alterations on MSCs phenotype but did increase indoleamine-2,3-dioxygenase (IDO), inducible costimulatory ligand (ICOSL), IL-1β, IL-8, and TNF-α mRNA expression.ConclusionsOverall, our study showed that MSCs differentially regulate the functional compartments of CD4+ and CD8+ T cells, which may differentially impact their therapeutic effect in immune disorders. Furthermore, the influence of MSCs on IL-9 expression can open new possibilities for MSC-based therapy in allergic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/scrt537) contains supplementary material, which is available to authorized users.

Dental follicle mesenchymal stem cells down‐regulate Th2‐mediated immune response in asthmatic patients mononuclear cells

“…Results indicated that the anti‐apoptotic effect of DFSCs in the cocultures suggests the suppressive effect of these cells on effector T lymphocyte subsets rather than apoptosis. Previous studies revealed that soluble and cell contact‐dependent mediators produced by MSCs suppress T‐cell activations and effector functions . In concordance with these studies, our results support the protective mechanism of DFSCs on naïve T lymphocyte population by suppressing antigen‐specific T lymphocyte activation during inflammatory responses.…”

ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells

“…ICOSL expression in MSCs has been reported by us and other groups163233. Here, we provide evidence that ICOSL expression in MSCs promotes CD4 + CD25 + FoxP3 + Treg induction.…”

Effect of Highly Active Antiretroviral Therapy on T-Cell Sub-population Profile in Human Immunodeficiency Virus-1 Infected Patients

“…Such progenitors initially appear in the liver by about six weeks of gestation, and then shift by about five months of gestation to the bone marrow, which is the major source of T cell progenitors throughout the remainder of life. Progenitor cells reach the thymus via the blood, entering into the thymus through venules near the cortico medullary junction and then migrating to the outer cortex [5,6]. Interaction of the T cell receptor (TCR) with cognate ligands in the thymus may result in either maturation (positive selection) or death (negative selection) [7] and critical parameter that controls the fate of a thymocytes seems to be the number of TCRs engaged with complexes of peptide and major histocompatibility complex [8].…”

“…For these reasons, it is important to provide some general background on the phenotypic markers and functions that are generally used to define populations of antigen (Ag) -specific T cells at different stages of differentiation prior to address in details the abnormalities observed in HIV infection [6,30].…”