Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.


Journal Article

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-gamma (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.

Full Text

Cited Authors

  • Guo, Z; Wang, J; Meng, L; Wu, Q; Kim, O; Hart, J; He, G; Zhou, P; Thistlethwaite, JR; Alegre, ML; Fu, YX; Newell, KA

Published Date

  • November 1, 2001

Published In

Volume / Issue

  • 167 / 9

Start / End Page

  • 4796 - 4800

PubMed ID

  • 11673481

Pubmed Central ID

  • 11673481

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.167.9.4796


  • eng

Conference Location

  • United States