Effects of Lipopolysaccharide on the Induction of Mixed Chimerism in Cyclophosphamide-Induced Tolerance

T. Onzuka, Y. Tomita, I. Shimizu, S. Okano, H. Yamada, Yasunobu Yoshikai, R. Tominaga

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    Cyclophosphamide (CP)-induced tolerance is a mixed chimerism-based tolerance and is one of the strategies used to induce transplant tolerance. Toll-like receptor (TLR) agonists are reportedly able to abrogate the induction of tolerance by activating alloreactive T cells, or by inhibiting Treg cells. However, little is known about the effect of the immune response mediated by TLR on mixed chimerism-based tolerance protocols. In this study, we evaluated the influence of lipopolysaccharide (LPS), which is best known as an TLR4 agonist, on CP-induced tolerance. BALB/c (H-2d) mice received a conditioning regimen consisting of 108 donor DBA/2 (H-2d) spleen cells (SC) on day 0 and 200 mg/kg CP on day 2. A single dose of 20 μg LPS was injected on day -2, 0, 7, or 35. Our results showed that LPS infusion at any time point resulted in chronic rejection of donor skin grafts and the abrogation of mixed chimerism in 33-60% of recipients. We found a correlation between skin graft acceptance and higher levels of mixed chimerism. Flow cytometric analysis revealed that donor-reactive T cells were permanently eliminated, regardless of LPS infusion. In conclusion, LPS-infusion had little influence on the immune response of donor-reactive T cells, but had a significant effect on the induction and maintenance of mixed chimerism in CP-induced tolerance.

    Original languageEnglish
    Pages (from-to)423-430
    Number of pages8
    JournalScandinavian Journal of Immunology
    Issue number5
    Publication statusPublished - Nov 2009

    All Science Journal Classification (ASJC) codes

    • Immunology


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