Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4+ T cell activation

Carrión, Flavio; Nova, Estefania; Luz, P. A. C.; Apablaza, Felipe; Figueroa, Fernando

doi:10.1016/j.imlet.2010.09.006

Cited by 71 publications

(66 citation statements)

References 23 publications

(33 reference statements)

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“…However, at lower ratios (i.e., 1:10), differences in IL-10 induction between MAPCs and MSCs were not apparent (data not shown). Although IL-10 induction and Th1 cytokine suppression are regarded as consensus properties for MSCs, suppression of Th17 cells remains more contentious, with discordant reports proposing that MSCs can enhance or inhibit Th17 expansion (42)(43)(44)(45)(46)(47)(48). It was suggested that this may reflect the influence of a network of interdependent variables, such as donor, cell type, licensing, T cell activation status, level of contact, and balance in Th17-enhancing (i.e., TGF-b/IL-6) versus inhibitory (e.g., IDO, PGE 2 ) factors (3,41).…”

Section: Discussionmentioning

confidence: 99%

Clinical-Grade Multipotent Adult Progenitor Cells Durably Control Pathogenic T Cell Responses in Human Models of Transplantation and Autoimmunity

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Yang

Sabbah

et al. 2013

The Journal of Immunology

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A major goal of immunotherapy remains the control of pathogenic T cell responses that drive autoimmunity and allograft rejection. Adherent progenitor cells, including mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells (MAPCs), represent attractive immunomodulatory cell therapy candidates currently active in clinical trials. MAPCs can be distinguished from MSCs on the basis of cellular phenotype, size, transcriptional profile, and expansion capacity. However, despite their ongoing evaluation in autoimmune and allogeneic solid organ transplantation settings, data supporting the immune regulatory potential of clinical-grade MAPCs are limited. In this study, we used allogeneic islet transplantation as a model indication to assess the ability of clinical-grade MAPCs to control T cell responses that drive immunopathology in human autoimmune disease and allograft rejection. MAPCs suppressed T cell proliferation and Th1 and Th17 cytokine production while increasing secretion of IL-10 and were able to suppress effector functions of bona fide autoreactive T cells from individuals with type 1 diabetes mellitus, including killing of human islets. Furthermore, MAPCs favored the proliferation of regulatory T cells during homeostatic expansion driven by γ-chain cytokines and exerted a durable, yet reversible, control of T cell function. MAPC suppression required licensing and proceeded via IDO-mediated tryptophan catabolism. Therefore, the common immune modulatory characteristics of clinical-grade MAPCs shown in this study suggest that they can be regarded as an alternative source of adult progenitor cells with similar clinical usefulness to MSCs. Taken collectively, these findings may guide the successful deployment of both MSCs and MAPCs for the amelioration of human autoimmunity and allograft rejection.

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Section: Discussionmentioning

confidence: 99%

Clinical-Grade Multipotent Adult Progenitor Cells Durably Control Pathogenic T Cell Responses in Human Models of Transplantation and Autoimmunity

Reading

Yang

Sabbah

et al. 2013

The Journal of Immunology

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“…As to IFN-g concentrations they were very similar in all culture conditions. Discussion BM-derived MSCs display, in vitro and in vivo, immunosuppressive activity on activated T cells [28], dendritic cells [29,30], and NK cells [31], whereas a direct immunomodulatory effect of MSCs on B cells is still a matter of controversy [9,11,26,32,33]. Similar experimental set-ups, from independent laboratories, using cocultures of MSCs and purified/sorted B cells stimulated with CpG, CD40L, anti-Ig antibodies, IL-2, IL-4, and IL-10 gave conflicting results for what concerns B-cell proliferation and antibody production [8,9,11].…”

Section: The Role Of Cell Contact and Soluble Factorsmentioning

confidence: 99%

Inhibition of B-Cell Proliferation and Antibody Production by Mesenchymal Stromal Cells Is Mediated by T Cells

Rosado

Bernardo

Scarsella

et al. 2015

Stem Cells and Development

135

110

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Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and antiinflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs + CpG. Inhibition is restored in CpG + MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4 + and CD8 + cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.

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“…For example, in one study MSCs exhibited their typical suppressive phenotype when added early to cell cultures in the presence of CD4(+) T cell polarizing stimuli. However, once T cell activation had occurred, MSCs showed an opposite stimulating effect on Th17 cells, while leaving T regulatory (Treg) IL-10-producing cells unchanged [34]. These results suggest that the therapeutic use of MSCs in vivo might exert opposing effects on disease activity, according to the time of therapeutic application and the level of effector T cell activation, especially in autoimmune disease models [34].…”

Section: Msc Time Of Administrationmentioning

confidence: 99%

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

Borjesson

Peroni

2011

Clinics in Laboratory Medicine

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Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4+ T cell activation

Cited by 71 publications

References 23 publications

Clinical-Grade Multipotent Adult Progenitor Cells Durably Control Pathogenic T Cell Responses in Human Models of Transplantation and Autoimmunity

Clinical-Grade Multipotent Adult Progenitor Cells Durably Control Pathogenic T Cell Responses in Human Models of Transplantation and Autoimmunity

Inhibition of B-Cell Proliferation and Antibody Production by Mesenchymal Stromal Cells Is Mediated by T Cells

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

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