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Robert Katamay, Baoying Liu, Zhiyu Li, Lai Wei, Robert B. Nussenblatt; Functional Mechanisms Of Concanavalin A (cona) Induced Regulatory T Cell Suppression In Humans. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2929.
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Regulatory T cells play a crucial role in maintaining an immuno-balance by modifying and inhibiting the functions of CD4(+) and CD8(+) effector T cells. It is known that ConA can induce suppressor cell activities in-vitro. The goal of this study is to investigate mechanisms of induced regulatory T cell function and its possible relevance in human diseases.
Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors using a Ficoll gradient centrifugation protocol. T cells were sorted out and pulsed with different doses of ConA in the presence and absence of monocytes. ConA induced regulatory T cells were cocultured with PBMCs in regular wells and in transwells. Their suppressive activity was measured using CFSE and radioactive proliferation assays. Intracellular staining followed by detection with a FACS Caliber flow cytometer was used to differentiate regulatory T cell populations. Single cell real-time polymerase chain reactions and microarray analyses were used to detect mRNA expression of cytokines.
Within 48 - 60 hours ConA induces dose dependently the expression of FOXP3 in human T cells. However, only in the presence of monocytes, those CD4(+) CD25(high) CD45RA(-) FOXP3(+) induced regulatory T cells achieved suppressive potency. Their level of CD39 does not change when being activated. After being cocultured with PBMCs they show clear suppression to both CD4(+) and CD8(+) T cells. The suppression lasts for more than 108 hours. It is mediated mainly through direct T cell to T cell interactions and to a smaller degree through cytokines.
During activation of T cells by ConA the presence of monocytes is necessary to induce the suppressive activity of regulatory T cells. They mediate their suppressive potency through direct T cell to T cell contact. Our data emphasize the importance of induced regulatory T cells and monocytes as regulatory players during activation.
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