Human multipotent stromal cells inhibit the activation of antigen specific murine CD4+ and CD8+ T cells (147.7)
| Autor: | Cristina Nazarov, Jessica LoSurdo, Steven Bauer, Cheng-Hong Wei |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:147.7-147.7 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.147.7 |
| Popis: | Multipotent stromal cells (MSCs) are known to have immunosuppressive activity. They do not induce allospecific T cell responses, making them promising tools for reducing the severity of graft vs host disease. Although the immunosuppressive effect has been extensively studied, the molecular mechanisms remain elusive. In our in vitro model, we culture CD4+ or CD8+ T cells from two T cell receptor transgenic mice strains together with human MSCs, followed by flow cytometry analysis of different activation markers present on T cells, real time RT-PCR for important transcription factors and ELISA for Th1 and Th2 cytokines. First, proliferation of both CD4+ and CD8+ T cells is clearly inhibited by human MSCs. These T cell subsets are, with some exceptions, similarly affected by MSCs. Both CD25 and CD69 activation markers are significantly inhibited on the surface of CD4+ and CD8+ T cells. Second, factors associated with a T regulatory phenotype (CTLA-4, CD62L) have an increased expression, while IFN-gamma and other cytokines are inhibited by MSCs in both T cell subsets. Third, real time RT-PCR data analysis showed that transcription factors Tbet and GATA3 are significantly inhibited by MSCs. Also, MSCs induce a slight increase in annexin V positive CD4+ T cells, but have no effect on the viability of CD8+ T cells. Moreover, the effects seem to be specific to MSCs; incubating the T cells with two different controls has no effect on T cell proliferation and activation. |
| Databáze: | OpenAIRE |
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