PD-1 tempers Tregs in chronic HCV infection.
Adaptive T cell responses are critical for controlling infections with viruses such as HIV, HBV, and HCV. However, these responses must be carefully regulated because overly vigorous T cell activation can lead to excessive host tissue damage. T cell expression of the inhibitory receptor programmed death-1 (PD-1) and inhibition of effector T cells (Teffs) by CD4+Foxp3+Tregs are among the many described mechanisms for achieving a balanced immune response. Although the signals that contribute to Teff function are well understood, less is known about the signals controlling Tregs. In this issue of the JCI, Franceschini et al. extend our understanding of how Tregs are modulated during chronic HCV infection by demonstrating that Treg proliferation is inhibited by PD-1 and that this inhibition is mediated by a potentially novel mechanism involving the prevention of IL-2-driven STAT-5phosphorylation.
Radziewicz
Henry
H
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Dunham
Richard M
RM
Grakoui
Arash
A
D015703:Antigens, CD / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D061026:Programmed Cell Death 1 Receptor; D050799:STAT5 Transcription Factor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D007376:Interleukin-2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D050799:STAT5 Transcription Factor