title: Global natural regulatory T cell depletion in active systemic lupus erythematosus.
abstract: The immune defect that could account for the multisystemic involvement that characterizes systemic lupus erythematosus (SLE) remains unknown. We hypothesized that iterative disease flares correspond to a recurrent defect in the peripheral immune suppression exerted by naturally occurring T regulatory cells (Tregs). Surprisingly, Tregs isolated from lupus patients show the same phenotypic and functional characteristics as corresponding cells found in healthy controls. A decrease in the proportion of circulating Tregs among other CD4+ T cells is nevertheless evidenced in active patients when this group is compared with healthy controls (0.57 +/- 0.24%, n = 45 vs 1.29 +/- 0.38%, n = 82, p < 0.0001) or with inactive patients (1.22 +/- 0.67%, n = 62, p < 0.0001). In contrast, the proportion of Tregs in other systemic autoimmune diseases such as primary Sjögren syndrome and inflammatory myopathy does not significantly differ from controls' values (1.15 +/- 0.46%, n = 21, p = 0.09 and 1.16 +/- 0.44%, n = 16, p = 0.43, respectively). Lupus Tregs do not accumulate in either the lymph nodes or the diseased kidneys and are not killed by a circulating soluble factor, but demonstrate in vitro a heightened sensitivity to Fas-induced apoptosis. Finally, we show that the extent of Treg depletion correlates with the clinical severity of the flare. SLE flares are therefore associated with a global Treg depletion and not with a phenomenon of tissue redistribution. In summary, we suggest that the physiopathology of SLE could be tied to a defect in the homeostatic control of the Treg subpopulation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 543, Immunologie A, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Karim
authors.initials: K
authors.lastname: Dorgham
authors.forename: Salim
authors.initials: S
authors.lastname: Trad
authors.forename: Dominique
authors.initials: D
authors.lastname: Nochy
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D014018:Tissue Distribution; D019014:fas Receptor
chemical_list: D019014:fas Receptor