Programmed death-1-induced interleukin-10 production by monocytes impairs CD4 + T cell activation during HIV infection

Elias A. Said, Franck P. Dupuy, Lydie Trautmann, Yuwei Zhang, Yu Shi, Mohamed El-Far, Brenna J. Hill, Alessandra Noto, Petronela Ancuta, Yoav Peretz, Simone G. Fonseca, Julien Van Grevenynghe, Mohamed R. Boulassel, Julie Bruneau, Naglaa H. Shoukry, Jean Pierre Routy, Daniel C. Douek, Elias K. Haddad, Rafick Pierre Sekaly

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266 Citations (Scopus)

Abstract

Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4 + T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4 + T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalNature Medicine
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 2010

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Said, E. A., Dupuy, F. P., Trautmann, L., Zhang, Y., Shi, Y., El-Far, M., Hill, B. J., Noto, A., Ancuta, P., Peretz, Y., Fonseca, S. G., Van Grevenynghe, J., Boulassel, M. R., Bruneau, J., Shoukry, N. H., Routy, J. P., Douek, D. C., Haddad, E. K., & Sekaly, R. P. (2010). Programmed death-1-induced interleukin-10 production by monocytes impairs CD4 + T cell activation during HIV infection. Nature Medicine, 16(4), 452-459. https://doi.org/10.1038/nm.2106