Journal article
RNF5-deficiency inhibits CD8+ T cell exhaustion in chronic antigen stimulation
The Journal of immunology (1950), v 206(1_Supplement), 14
01 May 2021
Abstract
Abstract Functional T cell exhaustion develops with persistent antigen exposure during chronic viral infection and cancer. Greater insights into T cell exhaustion are needed to promote immunity to viruses and tumors. RNF5 (RING-finger protein 5) is an E3 ubiquitin ligase that functions in protein degradation. We previously found enhanced anti-tumor responses in RNF5−/− mice, which was coupled with greater recovery and function of CD8+ T cell in melanoma tumors. Tumor-infiltrating RNF5−/− CD8+ T cells expressed high levels of inhibitory receptors (IR), yet greater functionality compared to WT CD8+ T cells, suggesting greater activation. To further assess RNF5-dependent regulation of CD8+ T cell exhaustion, we used the chronic LCMV Cl13 infection that has defined states of progressive T cell exhaustion. Virus-specific CD8+ T cells were significantly increased in RNF5−/− mice leading to greater numbers of cytokine producers, which expressed high levels of IRs. They also expressed higher levels of TOX, a transcriptional regulator of T cell exhaustion and persistence. With low dose infection, RNF5−/− mice displayed decreased morbidity and CD8+ T cells acquired a highly functional memory phenotype rather than exhaustion. To identify T cell intrinsic role(s) of RNF5, we analyzed anti-viral responses in bone marrow chimeras lacking RNF5 only in T cells and used an in vitro T cell exhaustion assay. RNF5−/− CD8+ T cells also expressed high levels of IRs and TOX, as did the in vitro exhausted T cells yet importantly displayed enhanced cytokine production compared to WT cells. These data reveal a T cell-intrinsic role of RNF5 in promoting exhaustion in settings of chronic antigen stimulation.
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Details
- Title
- RNF5-deficiency inhibits CD8+ T cell exhaustion in chronic antigen stimulation
- Creators
- Eun-ah Bae - Discovery InstituteJennifer L Hope - Sanford Burnham Prebys Medical Discovery InstituteDennis C Otero - Discovery InstituteHannah A Faso - Discovery InstituteAshley B Palete - Discovery InstituteZe’ev A Ronai - Discovery InstituteLinda M Bradley - Discovery Institute
- Publication Details
- The Journal of immunology (1950), v 206(1_Supplement), 14
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991021463672204721