One group of immune cells that help control viral infections are known as T cells. However, it is important to keep these cells under control, as overly vigorous T cell responses can lead to tissue damage, which has potentially serious health consequences.
Vincenzo Barnaba and colleagues, at Sapienza Università di Roma, Italy, have now provided new insight into the regulation of cells known as Tregs, which control the balance between an adequate antiviral immune response and suppression of tissue damage, in the livers of patients chronically infected with hepatitis C virus (HCV).
The research is published Feb. 23, 2009, in the Journal of Clinical Investigation.
In an accompanying commentary, Arash Grakoui and colleagues, at Emory University School of Medicine, Atlanta, discuss the clinical importance of these data.
In the study, although Tregs were found to accumulate at sites of infection in the livers of patients chronically infected with HCV, they were substantially fewer in number and proliferated less than effector T cells (the cells that control the viral infection). The level of expression of the protein PD-1 on Tregs inversely correlated with both their ability to proliferate and clinical markers of immune suppression in vivo. In vitro analysis indicated that blocking the interaction between PD-1 and PD-L1 enhanced the proliferation and suppressive function of Tregs from the livers of patients chronically infected with HCV, indicating that PD-L1 negatively regulates Tregs at sites of chronic inflammation.
Further analysis provided evidence of the mechanism underlying this: PD-L1 downregulates STAT-5 phosphorylation.
- Franceschini et al. PD-L1 negatively regulates CD4 CD25 Foxp3 Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI36604
- Grakoui et al. PD-1 tempers Tregs in chronic HCV infection. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38661
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