Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

Sara Bolivar-Wagers, Jemma H. Larson, Sujeong Jin, Bruce R. Blazar

Research output: Contribution to journalReview articlepeer-review


Regulatory T-cells (Treg) are critical for the maintenance of immune homeostasis and tolerance induction. While the immunosuppressive mechanisms of Treg have been extensively investigated for decades, the mechanisms responsible for Treg cytotoxicity and their therapeutic potential in regulating immune responses have been incompletely explored and exploited. Conventional cytotoxic T effector cells (Teffs) are known to be important for adaptive immune responses, particularly in the settings of viral infections and cancer. CD4+ and CD8+ Treg subsets may also share similar cytotoxic properties with conventional Teffs. Cytotoxic effector Treg (cyTreg) are a heterogeneous population in the periphery that retain the capacity to suppress T-cell proliferation and activation, induce cellular apoptosis, and migrate to tissues to ensure immune homeostasis. The latter can occur through several cytolytic mechanisms, including the Granzyme/Perforin and Fas/FasL signaling pathways. This review focuses on the current knowledge and recent advances in our understanding of cyTreg and their potential application in the treatment of human disease, particularly Graft-versus-Host Disease (GVHD).

Original languageEnglish (US)
Article number864748
JournalFrontiers in immunology
StatePublished - Apr 12 2022

Bibliographical note

Funding Information:
Authors were supported by funding from the National Institutes of Health. RO1 HL56067, R01 HL11879, R01 HL155114, R37 AI 34495, and P01 AI05662. T32 AI007313 and F30HL156312.

Publisher Copyright:
Copyright © 2022 Bolivar-Wagers, Larson, Jin and Blazar.


  • CAR T-cells
  • GVHD
  • cytotoxic
  • iTreg
  • pTreg
  • regulatory T-cell
  • tTreg

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural


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