CD152 (CTLA‐4) regulates effector functions of CD8+ T lymphocytes by repressing Eomesodermin

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Abstract
CD8+ T lymphocytes are required for effective host defense against pathogens and also for mediating effector responses against uncontrolled proliferating self-tissues. In this study, we determine that individual CD8+ T cells are tightly controlled in their effector functions by CD152 (CTLA-4). We demonstrate that signals induced by CD152 reduce the frequency of IFN-γ and granzyme B expressing CD8+ T cells independently of the transcription factors T-bet or cKrox by selectively inhibiting accumulation of Eomesodermin mRNA and protein. Ectopic expression of Eomesodermin reversed the CD152-mediated inhibition of effector molecule production. Additionally, enhanced cytotoxicity of individual CD8+ T cells differentiated in the absence of CD152 signaling was determined in vivo. These novel insights extend our understanding of how immune responses of CD8+ T cells are selectively modulated.
Funding Information
  • DFG (Br1860/3)
  • Charité-Universitätsmedizin Berlin (Germany)