Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells

Caserta, Stefano; Nausch, Norman; Sawtell, Amy; Drummond, Rebecca; Barr, Tom; MacDonald, Andrew S.; Mutapi, Francisca; Zamoyska, Rose

Abstract

Certain parasites have evolved to evade the immune response and establish chronic infections that may persist for many years. T cell responses in these conditions become muted despite ongoing infection. Upregulation of surface receptors with inhibitory properties provides an immune cell-intrinsic mechanism that, under conditions of chronic infection, regulates immune responses and limits cellular activation and associated pathology. The negative regulator, CD200 receptor, and its ligand, CD200, have been shown to regulate macrophage activation and reduce pathology following infection. We show that CD4 T cells also increase expression of inhibitory CD200 receptors (CD200R) in response to chronic infection. CD200R was upregulated on murine effector T cells in response to infection with bacterial, Salmonella enterica, or helminth, Schistosoma mansoni, pathogens that respectively drive predominant Th1- or Th2-responses. In vitro chronic and prolonged stimuli were required for the sustained upregulation of CD200R, and its expression coincided with loss of multifunctional potential in T effector cells during infection. Importantly, we show an association between IL-4 production and CD200R expression on T effector cells from humans infected with Schistosoma haematobium that correlated effectively with egg burden and, thus infection intensity. Our results indicate a role of CD200R:CD200 in T ce ll responses to helminths which has diagnostic and prognostic relevance as a marker of infection for chronic schistosomiasis in mouse and man. © 2012 Caserta et al.

Citation

Caserta, S., Nausch, N., Sawtell, A., Drummond, R., Barr, T., MacDonald, A. S., …Zamoyska, R. (2012). Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells. PLoS ONE, 7(4), e35466. https://doi.org/10.1371/journal.pone.0035466

• Journal Article Type: Article
• Acceptance Date: Mar 16, 2012
• Online Publication Date: Apr 9, 2012
• Publication Date: Apr 9, 2012
• Deposit Date: Jun 28, 2018
• Publicly Available Date: Jul 31, 2018
• Journal: PLoS ONE
• Print ISSN: 1932-6203
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 4
• Article Number: e35466
• Pages: e35466
• DOI: https://doi.org/10.1371/journal.pone.0035466
• Keywords: T cells; T helper cells; Cytokines; Helminth infections; Cell staining; Schistosoma mansoni; Schistosomiasis; Spleen
• Public URL: https://hull-repository.worktribe.com/output/620546
• Publisher URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035466