%0 Journal Article
%T The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion
%A Christine S. Falk
%A Claudia Pokoyski
%A Ildar Gabaev
%A Jasmin Zischke
%A Matthias Lochner
%A Panagiota Mamareli
%A Penelope C. Kay-Fedorov
%A Roland Jacobs
%A Sabine Buyny
%A Thomas F. Schulz
%A Tim Sparwasser
%J -
%D 2017
%R 10.1371/journal.ppat.1006454
%X Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host¡¯s immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus. The mechanisms by which HCMV affects T cell IL-10 secretion are not understood. We show here that treatment of PBMC with purified pUL11 induces IL-10 producing T cells as a result of pUL11 binding to the CD45 phosphatase on T cells. IL-10 production induced by HCMV infection is also in part mediated by pUL11. Supernatants from pUL11 treated cells have anti-inflammatory effects on untreated PBMC. Considering the mechanism, CD45 can be a positive or negative regulator of TCR signalling, depending on its expression level, and we show that pUL11 also has concentration dependent activating or inhibitory effects on T cell proliferation and on the kinase function of the CD45 substrate Lck. pUL11 is therefore the first example of a viral protein that can target CD45 to induce T cells with anti-inflammatory properties. It is also the first HCMV protein shown to induce T cell IL-10 secretion. Understanding the mechanisms by which pUL11-induced changes in signal strength influence T cell development and function may provide the basis for the development of novel antiviral treatments and therapies against immune pathologies
%K T cells
%K Phosphorylation
%K TCR signaling cascade
%K Cytomegalovirus infection
%K Human cytomegalovirus
%K Secretion
%K T helper cells
%K Tyrosine
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006454