title: Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells.
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.
authors.affiliation: Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caserta
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.forename: Amy
authors.initials: A
authors.lastname: Sawtell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Drummond
authors.forename: Tom
authors.initials: T
authors.lastname: Barr
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Macdonald
authors.forename: Francisca
authors.initials: F
authors.lastname: Mutapi
authors.forename: Rose
authors.initials: R
authors.lastname: Zamoyska
mesh_terms: D000293:Adolescent; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology*; D002478:Cells, Cultured; D002648:Child; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064446:Orexin Receptors; D011223:Praziquantel / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000276:immunology; D012548:Schistosoma haematobium / Q000276:immunology / Q000302:isolation & purification; D012550:Schistosoma mansoni / Q000276:immunology / Q000302:isolation & purification; D012552:Schistosomiasis / Q000188:drug therapy / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D000871:Anthelmintics; D015703:Antigens, CD; D000954:Antigens, Surface; C492346:CD200 receptor, mouse; C477337:CD200R1 protein, human; D008562:Membrane Glycoproteins; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D015847:Interleukin-4; D011223:Praziquantel; C042739:antigens, CD200