*Purpose: Preventing or reducing allograft rejection is critical in organ transplantation, and the need for immune modulation rather than immune suppression has been emphasized. Many studies have reported combinatorial therapies including thalidomide (TM) and dexamethasone (DX) can be used clinically for immune-related diseases, and in this study, we also suggest that TM and DX combinatorial treatments induce enhanced systemic immunomodulatory effects on T cells and dendritic cells (DCs) in regulating the expression of inhibitory molecules.

*Methods: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4⁺ T-cell proliferation and regulatory T cell (Treg) conversion in the presence of TM and/or DX. Expression of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 by splenic CD4⁺ T cells and expression of respective ligands by splenic DCs isolated from TM- and DX-treated mice.

*Results: Expression of CTLA-4 in Tregs in vitro significantly increased, as did that of CTLA-4 by Tregs and effector T cells in vivo with TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of CD80 and CD86 (ligands for CTLA-4) significantly increased in splenic DCs in TM/DX-treated groups. Moreover, TM/DX combinatorial treatment appears to activate the tolerogenic properties of DCs and therefore further induce immune tolerance, followed by overall systemic immunomodulation.

*Conclusions: In conclusion, we suggest that TM/DX combinatorial treatments are efficient immunomodulatory methods that exhibit promising capacity for maintaining a tolerogenic state or immune homeostasis.

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