Targeting LFA-1 synergizes with CD40/CD40L blockade for suppression of both CD4-dependent and CD8-dependent rejection

Yue Wang, Donghong Gao, Keri E. Lunsford, Wendy L. Frankel, Ginny L. Bumgardner

    Research output: Contribution to journalArticlepeer-review

    27 Scopus citations


    Allogeneic hepatocytes elicit CD4-dependent and (CD4-independent) CD8 + T-cell-initiated graft rejection. The (CD4-independent) CD8 + T-cell pathway is resistant to immunosuppressive strategies that readily and indefinitely suppress CD4+ T-cell-dependent rejection responses. Consequently, successful immunoregulation of hepatocyte-initiated immune responses requires a strategy which regulates both CD4-dependent and CD8-dependent rejection responses. Interference with CD40/CD40 ligand (CD40L) costimulation only transiently suppresses CD4- and CD8-dependent hepatocyte rejection. Interference with CD28/B7 costimulation transiently suppresses CD4-dependent hepatocyte rejection, but is ineffective for suppression of CD8-dependent hepatocyte rejection. To date, hepatocyte survival > 60 days post-transplant has not been achieved by any immunotherapeutic strategy. In the current study, we evaluated a novel immunosuppressive strategy which targets both LFA-1 and CD40L-mediated signals. Targeting LFA-1 suppressed (CD4-independent) CD8+ T-cell-initiated hepatocyte rejection such that allogeneic hepatocyte survival > 60 days was achieved in 70% of CD4 KO mice. Targeting both LFA-1-mediated signals and CD40/CD40L costimulation resulted in synergistic effects, such that hepatocellular survival > 60 days was achieved in 100% of C57BL/6 mice (which have both CD4- and CD8-dependent T-cell pathways available).

    Original languageEnglish (US)
    Pages (from-to)1251-1258
    Number of pages8
    JournalAmerican Journal of Transplantation
    Issue number10
    StatePublished - Oct 2003


    • Costimulation
    • Rodent
    • T lymphocytes
    • Transgenic/knockout
    • Transplantation

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Transplantation
    • Pharmacology (medical)


    Dive into the research topics of 'Targeting LFA-1 synergizes with CD40/CD40L blockade for suppression of both CD4-dependent and CD8-dependent rejection'. Together they form a unique fingerprint.

    Cite this