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Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection.

Publication ,  Journal Article
Mannon, RB; Griffiths, R; Ruiz, P; Platt, JL; Coffman, TM
Published in: Kidney Int
July 2002

BACKGROUND: In previous studies, we have demonstrated that a subset of mouse kidney allografts has prolonged survival without any immunosuppressive treatment. Chronic rejection (CR) develops in these long surviving grafts. The pathologic features of CR in this model are similar to CR in human kidney grafts. METHODS: To explore the role of donor major histocompatibility complex (MHC) antigens in the development of CR, we performed vascularized kidney transplants using kidneys from donor mice that lack expression of both MHC class I and II antigens (MHC-/-). RESULTS: Survival was significantly improved in recipients of MHC-/- allografts. This enhanced survival was associated with higher glomerular filtration rate (GFR) in MHC-/- allografts (4.92 +/- 0.54 cc/min/kg) compared to controls (2.19 +/- 0.63 cc/min/kg; P = 0.004). The typical histologic features of CR were markedly reduced in MHC-/- allografts. Semiquantitative histopathological scores for MHC-/- grafts (13.3 +/- 2.1) were significantly lower than in control allografts (19.0 +/- 1.0; P = 0.04). Along with this improvement in structural abnormalities, significantly fewer CD4+ T (38.3 cells/mm(2) vs. 75.0 cells/mm(2); P = 0.008), CD8+ T cells (38.7 vs. 96 cells/mm(2), respectively; P = 0.008) and macrophages (60 vs. 134 cells/mm(2), respectively; P = 0.04) infiltrated MHC-/- allografts compared to controls. The levels of intragraft cytokine mRNA expression also were reduced in MHC-/- allografts compared to control allografts. Finally, serum alloantibodies were virtually undetectable in recipients of MHC-/- kidney allografts. CONCLUSIONS: Cell surface expression of donor MHC antigens promotes the development of CR. Donor antigen expression promotes the accumulation of infiltrating cells in the graft and the development of donor specific alloantibodies. Abrogation of these responses is associated with improved graft survival and reduced CR in MHC-/- grafts.

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Published In

Kidney Int

DOI

ISSN

0085-2538

Publication Date

July 2002

Volume

62

Issue

1

Start / End Page

290 / 300

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation, Homologous
  • Transforming Growth Factor beta
  • RNA, Messenger
  • Mice, Inbred DBA
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Kidney
  • Isoantibodies
 

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Mannon, R. B., Griffiths, R., Ruiz, P., Platt, J. L., & Coffman, T. M. (2002). Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection. Kidney Int, 62(1), 290–300. https://doi.org/10.1046/j.1523-1755.2002.00422.x
Mannon, Roslyn B., Robert Griffiths, Phillip Ruiz, Jeffrey L. Platt, and Thomas M. Coffman. “Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection.Kidney Int 62, no. 1 (July 2002): 290–300. https://doi.org/10.1046/j.1523-1755.2002.00422.x.
Mannon RB, Griffiths R, Ruiz P, Platt JL, Coffman TM. Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection. Kidney Int. 2002 Jul;62(1):290–300.
Mannon, Roslyn B., et al. “Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection.Kidney Int, vol. 62, no. 1, July 2002, pp. 290–300. Pubmed, doi:10.1046/j.1523-1755.2002.00422.x.
Mannon RB, Griffiths R, Ruiz P, Platt JL, Coffman TM. Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection. Kidney Int. 2002 Jul;62(1):290–300.
Journal cover image

Published In

Kidney Int

DOI

ISSN

0085-2538

Publication Date

July 2002

Volume

62

Issue

1

Start / End Page

290 / 300

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Transplantation, Homologous
  • Transforming Growth Factor beta
  • RNA, Messenger
  • Mice, Inbred DBA
  • Mice, Inbred BALB C
  • Mice
  • Kidney Transplantation
  • Kidney
  • Isoantibodies