title: Novel biphasic role for lymphocytes revealed during resolving inflammation.
abstract: Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2). However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), gamma/delta T, CD4(+)/CD25(+), and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1(-/-) and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox(-/-) mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.
authors.affiliation: Department of Experimental Medicine and Translational Therapeutics, William Harvey Research Institute, London, United Kingdom.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Rajakariar
authors.forename: Toby
authors.initials: T
authors.lastname: Lawrence
authors.forename: Jonas
authors.initials: J
authors.lastname: Bystrom
authors.forename: Mark
authors.initials: M
authors.lastname: Hilliard
authors.forename: Paul
authors.initials: P
authors.lastname: Colville-Nash
authors.forename: Geoff
authors.initials: G
authors.lastname: Bellingan
authors.forename: Desmond
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob
authors.forename: Derek W
authors.initials: DW
authors.lastname: Gilroy
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D015230:Prostaglandin D2 / Q000494:pharmacology
chemical_list: D015230:Prostaglandin D2