Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 3, Pages 883-893Publisher
WILEY
DOI: 10.1002/eji.200838770
Keywords
CD8; Costimulation; Cytotoxicity; Inhibitory receptors; Transcription factors
Categories
Funding
- DFG [Br1860/3]
- Charite-Universitatsmedizin Berlin (Germany)
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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-gamma 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.
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