Impact of Immune-Modulatory Drugs on Regulatory T Cell

Abstract

Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4FOXP3 regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens. This review will discuss preclinical and clinical evidence regarding the influence of current and emerging immunosuppressive drugs on Treg homeostasis, stability, and function as a guideline for the selection and development of Treg-friendly immunosuppressive regimens.

Figure 1. Mechanisms of action of immunosuppressive drugs on T cell activation

Schematic representation of the mechanisms of action by which immunosuppressants control T cell activation. Black font marks molecules expressed by T cells and antigen presenting cells (APC). Red font marks immunosuppressive drugs. Black arrows indicate signaling pathways and red T-bars point to targets of immunosuppressive drugs.

Figure 2. Differential effects of immunosuppressive drugs on the balance between effector T cells and Treg

Immunosuppressive drugs are represented by colored blocks. The overall length of the block roughly correlates with the drug’s immunosuppressive potency. The left-right position of the block indicates the drug’s selectivity for effector T cells (Teff) versus Treg with the center position representing no selectivity and left to the center more suppressive for Teff than for Treg. The overall height of the balance in the cylinder below correlates with state of immune activity and the tilt of the balance correlates with regulatory activity.