Comparative Study of Immunomodulatory Agents to Induce Human T Regulatory (Treg) Cells: Preferential Treg-Stimulatory Effect of Prednisolone and Rapamycin

• Published in: Archivum Immunologiae et Therapiae Experimentalis Vol. 68; no. 4; p. 20
• Main Authors: Janyst, Michał, Kaleta, Beata, Janyst, Karolina, Zagożdżon, Radosław, Kozlowska, Ewa, Lasek, Witold
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 12.06.2020; Springer Nature B.V
• Subjects: Antigens; Antiviral drugs; Atorvastatin; Biomedical and Life Sciences; Biomedicine; CD25 antigen; CD4 antigen; Cell Differentiation; Cell Proliferation; Cells, Cultured; Copolymer 1; Forkhead Transcription Factors - metabolism; Foxp3 protein; Humans; Immunologic Factors - therapeutic use; Immunological tolerance; Immunology; Immunomodulation; Immunosuppression; Immunosuppressive agents; Interleukin-2 Receptor alpha Subunit - metabolism; Lymphocyte Activation; Lymphocytes T; Original; Original Article; Peripheral blood; Pharmacology/Toxicology; Prednisolone; Prednisolone - therapeutic use; Rapamycin; Self Tolerance; Sirolimus - therapeutic use; Sodium butyrate; T-Lymphocytes, Regulatory - immunology; Therapeutic applications; Transforming Growth Factor beta - metabolism; Glatiramer acetate; Atorvastatin; Treg cells; Rapamycin; Prednisolone; Inosine pranobex
• ISSN: 0004-069X; 1661-4917
• DOI: 10.1007/s00005-020-00582-6

T regulatory (Treg) cells play a critical role in the maintenance of self-tolerance, as well as in inhibition of inflammation and exaggerated immune response against exogenous antigens. They develop in the thymus (tTreg cells) but also may be generated at the peripheral tissues, including tumor microenvironment (pTreg cells), or induced in vitro in the presence of transforming growth factor (TGF)-β (iTreg cells). Since tTreg cells constitute a minor fraction of peripheral blood lymphocytes in physiological conditions, an alternative way to obtain high number of functional Treg cells for therapeutic purposes is their generation in vitro from conventional T cells. In our studies, we compared effectiveness of several pharmacological agents with suggested immunomodulatory effects on Treg development (rapamycin, prednisolone, inosine pranobex, glatiramer acetate, sodium butyrate, and atorvastatin) to optimize Treg-inducing protocols. All but one (atorvastatin) immunomodulators augmented induction of polyclonal Treg cells in cultures. They were effective both in increasing the number of CD4 + CD25 high Foxp3 high cells and Foxp3 expression. Rapamycin and prednisolone were found the most effective. Both drugs prolonged also phenotypic stability of Treg cells and induced fully active Treg cells in a functional assay. In the assay, prednisolone appeared superior versus rapamycin. The results, on the one hand, may be helpful in planning optimal protocols for generation of Treg cells for clinical application and, on the other hand, shed some light on mechanisms of the immunomodulatory activity of some tested agents observed in vivo.