Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells
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Purpose: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. Inthis study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be newapproaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitorymolecules. Materials and Methods: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferationand regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associatedantigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. Wealso quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/andDX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying outimmune responses. Results: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorialtreatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantlyincreased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolatedfrom TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. Conclusion: Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatorymethods for regulating T cell immunity.
Abstract
Purpose: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. Inthis study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be newapproaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitorymolecules. Materials and Methods: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferationand regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associatedantigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. Wealso quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/andDX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying outimmune responses. Results: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorialtreatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantlyincreased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolatedfrom TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. Conclusion: Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatorymethods for regulating T cell immunity.
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