Global natural regulatory T cell depletion in active systemic lupus erythematosus.
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.
Miyara
Makoto
M
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.
Amoura
Zahir
Z
Parizot
Christophe
C
Badoual
Cécile
C
Dorgham
Karim
K
Trad
Salim
S
Nochy
Dominique
D
Debré
Patrice
P
Piette
Jean-Charles
JC
Gorochov
Guy
G
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
D019014:fas Receptor