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CD44/CD70 Blockade and Anti‐CD154/LFA‐1 Treatment Synergistically Suppress Accelerated Rejection and Prolong Cardiac Allograft Survival in Mice
Author(s) -
Shao W.,
Yan G.,
Lin Y.,
Chen J.,
Dai H.,
Wang F.,
Xi Y.,
Thorlacius H.,
Qi Z.
Publication year - 2011
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2011.02595.x
Subject(s) - cd154 , blockade , adoptive cell transfer , il 2 receptor , effector , immunology , cytotoxic t cell , cd44 , cd8 , t cell , cd40 , cancer research , biology , medicine , immune system , in vitro , receptor , biochemistry
Current treatments that are efficient in controlling effector T cell responses to allografts have limited efficacy on the accelerated rejection mediated by memory T cells. Effective targeting of alloreactive memory T cells may therefore be explored to improve therapeutic approaches towards solving this problem. In this study, we investigated the synergistic effect of CD44/CD70 blockade and anti‐CD154/LFA‐1 treatment on the accelerated rejection mediated by memory T cells. While CD44/CD70 blockade had limited effects on the alloresponses of effector T cells in vivo , it diminished the expansion of both CD4 + and CD8 + memory T cells in recipients adoptively transferred with donor‐sensitized T cells. In combination with anti‐CD154/LFA‐1 treatment, CD44/CD70 blockade significantly prolonged cardiac allograft survival in adoptive transfer recipients. We demonstrated that treatment with the combination of all four antibodies (anti‐CD154/LFA‐1/CD44/CD70) inhibited accelerated rejection by markedly suppressing the alloresponses of effector and memory T cells and reducing the number of graft‐infiltration lymphocytes in adoptive transfer recipients. Meanwhile, CD44/CD70 blockade and anti‐CD154/LFA‐1 treatment synergically enhanced regulatory T cells (Tregs) by increasing the proportion of splenic Tregs and the expression of IL‐10 in these recipients. Our findings contribute to the potential design of therapies for accelerated allograft rejection.