Combined Costimulation Blockade Inhibits Accelerated Rejection Mediated by Alloantigen-primed Memory T Cells in Mice

Baiyi Xie, Jibing Chen, Junjie Xia, Yongzhi Wang, Hua Liang, Henrik Ekberg, Matthias Corbascio, Zhongquan Qi

    Research output: Contribution to journalArticlepeer-review

    10 Citations (SciVal)

    Abstract

    Donor-reactive memory T cells threaten the survival of transplanted organs via multiple pathways. This study was undertaken to induce tolerance of cardiac allografts in mice, in which alloreactive memory T cells were adoptively transferred, by combined costimulatory blockade of both effector and memory T cells. We found that the median survival time (MST) of the grafts was 5.17 days in the untreated group, 10.33 days in the CTLA4Ig- and antiCD40L- treated (2-combined) group, and more than 100 days in the CTLA4Ig-, anti-CD40L-, anti-LFA-1-, and anti-OX40L-treated (4-combined) group. Histological analysis revealed that the mean rejection level was Grade 4 in the untreated group, Grade 3 in the 2-combined treatment group, and Grade 0 in the 4-combined treatment group. CD44(high) T cells were detected only in the untreated group. The in vitro proliferation of lymphocytes of both untreated and 2-combined group was higher than that of the 4-combined treatment group (p < 0.01). Compared with the untreated group, the expression levels of IL-2, IFN-gamma, and Foxp3 were lower in the 2-combined treatment group; the expression levels of these genes were the lowest in the 4-combined treatment group. IL-10 expression was significantly higher in the 4-combined treatment group than in the other groups. These results demonstrate the inhibition efficacy of combined costimulation blockade in accelerated-rejection models and the possible mechanisms underlying the suppression of cellular immunity in mice receiving grafts as well as in inducing the activation of IL-10-producing Tr1 cells in grafts.
    Original languageEnglish
    Pages (from-to)639-651
    JournalImmunological Investigations
    Volume38
    Issue number7
    DOIs
    Publication statusPublished - 2009

    Subject classification (UKÄ)

    • Urology and Nephrology

    Keywords

    • Immunological tolerance
    • transplantation
    • Cardiac
    • Memory T cells
    • Costimulation blockade
    • Accelerated rejection

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