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

• Published in: European journal of immunology Vol. 39; no. 3; pp. 883 - 893
• Main Authors: Hegel, Johannes K, Knieke, Karin, Kolar, Paula, Reiner, Steven L, Brunner-Weinzierl, Monika C
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.03.2009; WILEY‐VCH Verlag
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - metabolism; CD8; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Costimulation; CTLA-4 Antigen; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene Expression Regulation; Granzymes - immunology; Granzymes - metabolism; Inhibitory receptors; Interferon-gamma - immunology; Interferon-gamma - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - immunology; Signal Transduction - immunology; T-Box Domain Proteins - genetics; Transcription factors
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200838770

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.