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 and Zamoyska, Rose (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. ISSN 1932-6203

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

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 cell responses to helminths which has diagnostic and prognostic relevance as a marker of infection for chronic schistosomiasis in mouse and man.

Item Type: Article
Keywords: T cells; schistosomiasis; Th2 differentiation; immunoregulation; CD200; CD200R
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: Q Science > QR Microbiology > QR0180 Immunology
Depositing User: Stefano Caserta
Date Deposited: 30 Sep 2015 06:51
Last Modified: 16 Mar 2017 23:11
URI: http://sro.sussex.ac.uk/id/eprint/56873

View download statistics for this item

📧 Request an update