TY - JOUR
T1 - Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice
AU - Kang, Xiangpeng
AU - Chen, Jibing
AU - Qin, Qing
AU - Wang, Feng
AU - Wang, Yongzhi
AU - Lan, Tianshu
AU - Xu, Shuo
AU - Wang, Feiyu
AU - Xia, Junjie
AU - Ekberg, Henrik
AU - Qi, Zhongquan
AU - Liu, Zhongchen
PY - 2010
Y1 - 2010
N2 - Memory T cells present a unique challenge in transplantation. Although memory T cells express robust immune responses to invading pathogens. they may be resistant to the effects of immunosuppressive therapies used to prolong graft survival. In previous studies, we found that compound K. the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., reduced acute cardiac allograft rejection in mice (Wang et al., 2009 [1]). Here, we further investigated the effect of compound K on cardiac allograft rejection in alloantigen-primed mice. We found that compound K significantly inhibited CD4(+) and CD8(+) memory T cells proliferation in a mixed lymphocyte reaction (MLR). In vivo, compound K combined with anti-CD154 and anti-LFA-1 monoclonal antibodies (mAbs) significantly extended the survival time of heart grafts in alloantigen-primed mice with no obvious toxic side effects. Furthermore, our data suggests that compound K works by reducing the expression of both IL-2 and IFN-gamma within the graft rather than enhancing expression of regulatory T cells (Tregs). Compound K can also inhibit the alloresponses of memory T cells, while increasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing the level of alloantibodies in the serum. Our study highlights the unique immune effects of compound K that may be further explored for clinical use in extending the survival of transplant grafts. (C) 2010 Elsevier B.V. All rights reserved.
AB - Memory T cells present a unique challenge in transplantation. Although memory T cells express robust immune responses to invading pathogens. they may be resistant to the effects of immunosuppressive therapies used to prolong graft survival. In previous studies, we found that compound K. the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., reduced acute cardiac allograft rejection in mice (Wang et al., 2009 [1]). Here, we further investigated the effect of compound K on cardiac allograft rejection in alloantigen-primed mice. We found that compound K significantly inhibited CD4(+) and CD8(+) memory T cells proliferation in a mixed lymphocyte reaction (MLR). In vivo, compound K combined with anti-CD154 and anti-LFA-1 monoclonal antibodies (mAbs) significantly extended the survival time of heart grafts in alloantigen-primed mice with no obvious toxic side effects. Furthermore, our data suggests that compound K works by reducing the expression of both IL-2 and IFN-gamma within the graft rather than enhancing expression of regulatory T cells (Tregs). Compound K can also inhibit the alloresponses of memory T cells, while increasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing the level of alloantibodies in the serum. Our study highlights the unique immune effects of compound K that may be further explored for clinical use in extending the survival of transplant grafts. (C) 2010 Elsevier B.V. All rights reserved.
KW - Isatis tinctoria L.
KW - Memory T cells
KW - Alloantigen-primed mice
U2 - 10.1016/j.trim.2010.03.006
DO - 10.1016/j.trim.2010.03.006
M3 - Article
C2 - 20338239
SN - 1878-5492
VL - 23
SP - 34
EP - 39
JO - Transplant Immunology
JF - Transplant Immunology
IS - 1-2
ER -