Cutting edge: Membrane lymphotoxin regulates CD8+ T cell-mediated intestinal allograft rejection

Z. Guo, J. Wang, L. Meng, Q. Wu, O. Kim, J. Hart, G. He, P. Zhou, Jr Thistlethwaite, M. L. Alegre, Y. X. Fu, K. A. Newell

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4+ T cells are necessary for rejection. When CD8+ T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8+ T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8+ T cells. This effect was associated with decreased monokine induced by IFN-γ (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4+ T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8+ T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.

Original languageEnglish (US)
Pages (from-to)4796-4800
Number of pages5
JournalJournal of Immunology
Volume167
Issue number9
DOIs
StatePublished - Nov 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Guo, Z., Wang, J., Meng, L., Wu, Q., Kim, O., Hart, J., He, G., Zhou, P., Thistlethwaite, J., Alegre, M. L., Fu, Y. X., & Newell, K. A. (2001). Cutting edge: Membrane lymphotoxin regulates CD8+ T cell-mediated intestinal allograft rejection. Journal of Immunology, 167(9), 4796-4800. https://doi.org/10.4049/jimmunol.167.9.4796