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

Hyung Ran Kim, Jeong Hae Kie, Woosung Lim, Byung In Moon, Seung Cheol Kim, Ju Young Seoh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.Conclusion. 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.

Original languageEnglish
Article numberkes058
Pages (from-to)1357-1367
Number of pages11
JournalRheumatology (United Kingdom)
Volume51
Issue number8
DOIs
StatePublished - Aug 2012

Bibliographical note

Funding Information:
Funding: This work was supported by the Korea Research Foundation (KRF) grant funded by the Korea government (MEST) (No. 2009-0073139) and by RP-Grant 2010 of Ewha Womans University.

Keywords

  • Adriamycin-nephropathy
  • Lupus
  • MRL/lpr mouse
  • Regulatory T cells
  • Suppressive activity

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