Manipulation of regulatory T-cell function by immunomodulators: a boon or a curse?
Regulatory T cells (Tregs) constitute a subset of lymphocytes that have the capability of suppressing immune responses in vivo and in vitro both directly by cell-cell contact and indirectly through the production of anti-inflammatory cytokines, such as interleukin-10 and tumor growth factor-β. Tregs constitute a small subset of T lymphocytes, yet their presence can prevent and control autoimmune disease and organ transplant rejection and contribute to maternal tolerance of fetal alloantigens, whereas their absence results in uncontrolled inflammation. But Treg function may not always be considered beneficial: There is growing evidence that the immunosuppressive effects of Tregs are also associated with growth of tumor cells. Thus, Tregs are of considerable medical interest as targets for the treatment of both inflammatory diseases and cancer. In this review of published literature, we describe some well-characterized immunomodulatory drugs and environmental toxicants that can either positively or negatively affect the number and/or function of Tregs in animal models and/or human patients. The targeted suppression or enhancement of Treg function needs to be carefully considered in immunotoxicity evaluations as manipulation of this immune cell population could result in undesired consequences, including decreased host resistance, decreased fertility, or increased incidence of inflammatory disease.
Fort
Madeline M
MM
Investigative Toxicology, Amgen Inc., Seattle, Washington 98119, USA.
Narayanan
Padma K
PK
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000633:toxicity*; D051379:Mice; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007155:Immunologic Factors