The Third Signal Cytokine IL-12 Rescues the Anti-Viral Function of Exhausted HBV-Specific CD8 T Cells

PLoS Pathogens

Patrick T. Kennedy¹  Eleni Nastouli¹  Upkar S. Gill²  William Rosenberg²  Mala K. Maini²  Sudeep Tanwar³  Anna Schurich⁴  Marcin Lubowiecki⁴  Harsimran D. Singh⁴  Laura J. Pallett⁴ 

[1] Centre for Digestive Disease, Barts and the London School for Medicine and Dentistry, London, United Kingdom;Centre for Hepatology, University College London, London, United Kingdom;Department of Clinical Microbiology and Virology, University College London Hospital, London, United Kingdom;Division of Infection and Immunity, University College London, London, United Kingdom

关键词: T cells;    Cytotoxic T cells;    Cytokines;    Cell staining;    Viral transmission;    infection;    Immune receptor signaling;    Viral persistence;    latency;    T cell receptors;   

DOI  :  10.1371/journal.ppat.1003208

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Optimal immune activation of naïve CD8 T cells requires signal 1 mediated by the T cell receptor, signal 2 mediated by co-stimulation and signal 3 provided by pro-inflammatory cytokines. However, the potential for signal 3 cytokines to rescue anti-viral responses in functionally exhausted T cells has not been defined. We investigated the effect of using third signal cytokines IL-12 or IFN-α to rescue the exhausted CD8 T cell response characteristic of patients persistently infected with hepatitis B virus (HBV). We found that IL-12, but not IFN-α, potently augmented the capacity of HBV-specific CD8 T cells to produce effector cytokines upon stimulation by cognate antigen. Functional recovery mediated by IL-12 was accompanied by down-modulation of the hallmark inhibitory receptor PD-1 and an increase in the transcription factor T-bet. PD-1 down-regulation was observed in HBV but not CMV-specific T cells, in line with our finding that the highly functional CMV response was not further enhanced by IL-12.

【 授权许可】

CC BY