Upregulation of Molecules Associated With T-Regulatory Function by Thymoglobulin Pretreatment of Human CD4+ Cells
This study evaluated the immunologic effects of thymoglobulin in modulating human CD4+ cells. Human CD4+ cells were purified from peripheral blood mononuclear cells by negative selection method. CD4+ cells were pretreated with thymoglobulin and incubated for 72 hr. Cells and culture supernatants wer...
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Veröffentlicht in: | Transplantation 2008-11, Vol.86 (10), p.1419-1426 |
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Sprache: | eng |
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Zusammenfassung: | This study evaluated the immunologic effects of thymoglobulin in modulating human CD4+ cells.
Human CD4+ cells were purified from peripheral blood mononuclear cells by negative selection method. CD4+ cells were pretreated with thymoglobulin and incubated for 72 hr. Cells and culture supernatants were collected and studied by real-time quantitative polymerase chain reaction, fluorescence activated cell scanning, multiplex cytokine assay, and mixed lymphocyte reaction (MLR).
Thymoglobulin pretreated CD4+ cells demonstrated up-regulation of gene transcripts for CTLA-4, OX40, forkhead box P3 (Foxp3), CD25, IFN-gamma, IL-10, and IL-2 as determined by real-time quantitative polymerase chain reaction. Fluorescence-activated cell scanning analysis demonstrated that CD4+ cells, pretreated with thymoglobulin, up-regulated CD25 expression on their surface, and the surface expression of CTLA-4 and OX40 and the expression of intracellular Foxp3 were observed in these CD4+CD25+ cells. Additionally, MLR demonstrated that thymoglobulin-pretreated cells partially inhibited proliferation of untreated autologous CD4+ cells in response to allogeneic cells. The high levels of IFN-gamma, IL-10, IL-2, and IL-4 were detected by multiplex cytokine assay in supernatants collected from cultures of thymoglobulin-pretreated CD4+ cells. The lymphocyte proliferation of allogeneic MLR was also partially blocked in the presence of supernatants from cultures of thymoglobulin-pretreated CD4+ cells.
This study demonstrates that the unique effects of thymoglobulin in modulating CD4+ cells may be an important mechanism for its action in inducing immunosuppression and transplant tolerance. |
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ISSN: | 0041-1337 1534-6080 |
DOI: | 10.1097/TP.0b013e318187c2e5 |