title: FoxP3+ regulatory T cells suppress early stages of granuloma formation but have little impact on sarcoidosis lesions.
abstract: Sarcoidosis is characterized by a disproportionate Th1 granulomatous immune response in involved organs. It is also associated with both peripheral and intratissular regulatory T cell (Treg) expansion. These cells exhibit powerful antiproliferative activity, yet do not completely inhibit the production of either tumor necrosis factor-alpha or interferon-gamma. The origin of the observed Treg amplification and, more importantly, its impact on the evolution of sarcoidosis remain unresolved issues. Here, we show that CD4(+)CD45RA(-)FoxP3(bright) Tregs proliferate and accumulate within granulomas. However, circulating and tissue Treg numbers are neither correlated with the dissemination of the disease nor correlated locally with the extent of granulomatous inflammation. Rather, we found a positive correlation between the presence of Tregs in renal granulomas and the degree of interstitial fibrosis (r = 0.46, P = 0.03, n = 20). Furthermore, Treg depletion accelerates in vitro granuloma growth in mononuclear cell cultures of healthy controls, but not in those from patients with active sarcoidosis. The results of this study show that although healthy Tregs suppress the initial steps of granuloma formation, they have no positive influence on sarcoidosis lesions. Our findings argue for a more preventive than curative effect of Tregs on inflammatory processes.
authors.affiliation: INSERM UMR-S 945, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Taflin
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
authors.forename: Dominique
authors.initials: D
authors.lastname: Nochy
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Naccache
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
authors.forename: Pascale
authors.initials: P
authors.lastname: Salek-Peyron
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Gary
authors.initials: G
authors.lastname: Hill
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors