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Prolonged survival of class II transactivator-deficient cardiac allografts.

Publication ,  Journal Article
June Brickey, W; Felix, NJ; Griffiths, R; Zhang, J; Wang, B; Piskurich, JF; Itoh-Lindstrom, Y; Coffman, TM; Ting, JP-Y
Published in: Transplantation
November 15, 2002

BACKGROUND: Major histocompatibility complex (MHC) antigenic complexes trigger allogeneic T-cell responses and allograft rejection. MHC class II and related antigen processing genes, such as invariant chain (Ii) and H2-DM accessory molecules, are controlled by the master transcriptional regulator, class II transactivator (CIITA). CIITA also up-regulates MHC class I gene expression in vitro. Thus, disruption of a single factor, namely CIITA, represents an ideal strategy for reducing transplant rejection. METHODS: We studied the immunological advantages of transplanting CIITA deficient hearts into mismatched recipients in comparison to wild-type (B6) allografts or MHC class II-deficient (Abeta ) hearts. RESULTS: Elimination of CIITA greatly enhanced graft survival (median survival time [MST] 36 days) over the survival of wild-type (MST 9 days) and even over Abeta (MST 20 days) cardiac grafts. This was accompanied by greatly reduced mixed lymphocyte reactivity and in vivo antigen priming capacity. Analyses for CD4, CD8, and other inflammatory cells, plus cytotoxic T-cell activity and MHC class I specific alloantibody production, did not reveal significant differences in CIITA allograft tissues. Some cytokines that may support immunosuppression, such as transforming growth factor (TGF)-beta, were increased in mice receiving either Abeta or CIITA cardiac grafts. CONCLUSIONS: We conclude that disruption of CIITA function plays a beneficial role in preventing normal allogeneic T-cell responses. Even though inflammatory cells are present in CIITA allografts, the dramatic prolongation in allograft survival of CIITA hearts as compared with wild-type grafts provides a foundation for designing molecular therapies to interfere with MHC class II function and thereby reduce transplantation rejection.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 15, 2002

Volume

74

Issue

9

Start / End Page

1341 / 1348

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transforming Growth Factor beta
  • Trans-Activators
  • Time Factors
  • T-Lymphocytes, Cytotoxic
  • Surgery
  • Nuclear Proteins
  • Myocardium
  • Mice, Knockout
  • Mice, Inbred Strains
 

Citation

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MLA
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June Brickey, W., Felix, N. J., Griffiths, R., Zhang, J., Wang, B., Piskurich, J. F., … Ting, J.-Y. (2002). Prolonged survival of class II transactivator-deficient cardiac allografts. Transplantation, 74(9), 1341–1348. https://doi.org/10.1097/00007890-200211150-00024
June Brickey, W., Nathan J. Felix, Robert Griffiths, Jinghua Zhang, Bo Wang, Janet F. Piskurich, Yoshie Itoh-Lindstrom, Thomas M. Coffman, and Jenny P-Y Ting. “Prolonged survival of class II transactivator-deficient cardiac allografts.Transplantation 74, no. 9 (November 15, 2002): 1341–48. https://doi.org/10.1097/00007890-200211150-00024.
June Brickey W, Felix NJ, Griffiths R, Zhang J, Wang B, Piskurich JF, et al. Prolonged survival of class II transactivator-deficient cardiac allografts. Transplantation. 2002 Nov 15;74(9):1341–8.
June Brickey, W., et al. “Prolonged survival of class II transactivator-deficient cardiac allografts.Transplantation, vol. 74, no. 9, Nov. 2002, pp. 1341–48. Pubmed, doi:10.1097/00007890-200211150-00024.
June Brickey W, Felix NJ, Griffiths R, Zhang J, Wang B, Piskurich JF, Itoh-Lindstrom Y, Coffman TM, Ting JP-Y. Prolonged survival of class II transactivator-deficient cardiac allografts. Transplantation. 2002 Nov 15;74(9):1341–1348.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 15, 2002

Volume

74

Issue

9

Start / End Page

1341 / 1348

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transforming Growth Factor beta
  • Trans-Activators
  • Time Factors
  • T-Lymphocytes, Cytotoxic
  • Surgery
  • Nuclear Proteins
  • Myocardium
  • Mice, Knockout
  • Mice, Inbred Strains