title: Regulatory T cells require renal antigen recognition through the TCR to protect against injury in nephritis.
abstract: Regulatory T cells (Treg) are important for maintaining immune homeostasis. Adoptive transfer of Tregs is protective in renal disease models in both immunocompetent and immunodeficient mice. However the involvement of TCR recognition of renal antigens remains to be clarified. To address this question, we made use of Tregs from the DO11.10 mouse (a TCR transgenic (Tg) mouse), that recognise the non-murine antigen Ovalbumin (OVA) and therefore are not activated by renal antigens. DO11.10 Tregs were assessed functionally in vitro and demonstrated equivalent suppression to WT BALB/c Tregs. Adriamycin Nephropathy (AN) was induced in mice which had been transfused with CD4+CD25+Tregs isolated from DO11.10 or BALB/c mice. To eliminate the memory/activation state as a cause of differences in activity, the protective capacity of DO11.10 Tregs pre-activated with OVA in vivo was assessed. Transfer of WT BALB/c Tregs significantly attenuated the development of AN with less glomerulosclerosis, tubular atrophy and macrophage infiltration as compared to AN mice without Treg transfer. However, mice receiving either naïve or pre-activated DO11.10 Tregs were not protected from AN. The lack of protection by DO11.10 Tregs was not due to failure to traffic to the affected kidney. These results suggest that antigen recognition in the kidney is important for Treg protection against injury.
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead Westmead, NSW 2145, Australia.
authors.forename: Yuanmin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Thian Kui
authors.initials: TK
authors.lastname: Tan
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Sora
authors.initials: S
authors.lastname: Lee
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead Westmead, NSW 2145, Australia.
authors.forename: Geoff Yu
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Changqi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Flow Cytometry Facility, Westmead Millennium Institute for Medical Research Westmead, NSW 2145, Australia.
authors.forename: Xin Maggie
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead Westmead, NSW 2145, Australia.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute Sydney, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Harris
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009393:Nephritis / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
keywords: Adriamycin Nephropathy; DO11.10 Tregs; antigen specificity