title: CD4⁺CD25⁺ regulatory T cells from MRL/lpr mice were functionally more active in vitro but did not prevent spontaneous as well as adriamycin-induced nephropathy in vivo.
abstract: OBJECTIVE
  The frequency and function of Tregs are important in the pathogenesis of SLE. Nonetheless, the function of Tregs is still controversial in SLE patients and lupus mouse models. In the present study, we investigated the suppressive function of Tregs from MRL/lpr mice in vitro and in vivo by using an alternative quantitative assay.
  
  
  METHODS
  We assessed the suppressive function of CD4(+)CD25(+) Tregs, the proliferative activity of CD4(+)CD25(-) effector T cells (Teffs) and the feeder activity of CD11c(+) dendritic cells (DCs), isolated from the spleens of MRL/lpr mice and wild-type (WT) MRL/+ mice, by carboxyfluorescein diacetate succinimidyl ester dilution assay stimulated with two distinct types of signals, weak and strong. In order to assess the protective function of Tregs from an immune-mediated disease in vivo, we induced renal damage by injecting adriamycin (ADN) into the mice.
  
  
  RESULTS
  The in vitro assay showed enhanced suppressive activity of Tregs and feeder activity of DCs, but far less proliferative activity of Teffs from MRL/lpr mice, compared with those from the WT mice. The in vivo study showed more severe ADN-induced nephropathy in MRL/lpr mice than in the WT mice, while mild interstitial nephritis had already begun spontaneously by 16 weeks in MRL/lpr mice.
  
  
  CONCLUSIONS
  It was suggested that Tregs from MRL/lpr mice were functionally competent and intrinsically more active in vitro, but they were not capable of preventing the ADN-induced as well as the spontaneously developing nephropathy in vivo.
authors.affiliation: Department of Microbiology, Ewha Womans University Medical School, Mok-6-Dong 911-1, Yangchon-Gu, Seoul 158-710, South Korea.
authors.forename: Hyung-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Jeong-Hae
authors.initials: JH
authors.lastname: Kie
authors.forename: Woosung
authors.initials: W
authors.lastname: Lim
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Moon
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004317:Doxorubicin; D066298:In Vitro Techniques; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D004317:Doxorubicin