| 1. |
- Shao, Wei, et al.
(författare)
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CD44/CD70 blockade and anti-CD154/LFA-1 treatment synergistically suppress accelerated rejection and prolong cardiac allograft survival in mice.
- 2011
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 74, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- Current treatments that are efficient in controlling effector T cells 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.
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| 2. |
- Shao, Wei, et al.
(författare)
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Combination of monoclonal antibodies with DST inhibits accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice
- 2011
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Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478. ; 138:2, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Donor-reactive memory T cells mediated accelerated rejection is known as a barrier to the survival of transplanted organs. We investigated the combination of different monoclonal antibodies (mAbs) and donor-specific transfusion (DST) in memory T cells-based adoptive mice model. In the presence of donor reactive memory T cells, the mean survival time (MST) of grafts in the anti-CD40L/LFA-1/DST group was 49.8 d. Adding anti-CD44/CD70 mAbs to anti-CD40L/LFA-1/DST treatment. The MST was more than 100 d (MST > 100 d). Compared with anti-CD40L/LFA-1/DST group, anti-CD40L/LFA-1/CD44/CD70/DST group notably reduced the expansion of memory T cells, enhanced the proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) and suppressed donor-specific responses. Our data suggest that anti-CD40L/LFA--1/CD44/CD70 mAbs and DST can synergistically inhibit accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice. (C) 2011 Elsevier B.V. All rights reserved.
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| 3. |
- Wang, Feng, et al.
(författare)
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Anti-CD44 Monoclonal Antibody Inhibits Heart Transplant Rejection Mediated by Alloantigen-primed CD4(+) Memory T Cells in Nude Mice
- 2010
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Ingår i: Immunological Investigations. - : Informa UK Limited. - 0882-0139 .- 1532-4311. ; 39:8, s. 807-819
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Tidskriftsartikel (refereegranskat)abstract
- Donor-reactive CD4(+) memory T cells threaten the survival of transplanted organs. In this study, we used anti-CD44 monoclonal antibody (mAb) to inhibit adoptively transferred B6-reactive CD4(+) memory T cells (BALB/c origin) and to induce tolerance of B6 hearts in nude mice. The median survival time (MST) of the grafts was 6 days in the isotype group, and more than 100 days in the group treated with 8 doses of anti-CD44 at four-day intervals. Histological analysis revealed that the mean rejection level was Grade 3 in the isotype group, and Grade 0 or 1 in the multi-dose anti-CD44 treatment group. Compared with the isotype group, the multiply treated anti-CD44 group had significantly decreased IL-2 and IFN-gamma expressions, while IL-10 and TGF-beta were increased in the serum and the graft. Foxp3 in the graft was also increased. These data demonstrate that alloreactive CD4(+) memory T cells mediate the destruction of allografts, and the adhesion molecule CD44 plays an important role in this course. Anti-CD44 mAb may promote the reduction of CD4(+) memory T cells and the production of regulatory T cells (Tregs). Furthermore, Tregs are maintained at a certain level while suppressing cellular immunity and inducing the grafts long-term survival in transplant recipients.
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| 4. |
- Wang, Feng, et al.
(författare)
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The major histocompatibility complex (MHC) of the secondary transplant tissue donor influences the cross-reactivity of alloreactive memory cells.
- 2011
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 73, s. 190-197
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Tidskriftsartikel (refereegranskat)abstract
- Memory cells are currently thought to be a major barrier to tolerance induction in transplantation. However, whether alloreactive memory cells resulting from a primary transplant have cross-reactivity in a second transplant is unclear. Here, we used skin transplantation from BALB/c mice donors to pre-sensitize C(57) BL/6 (B6) mice. One month later, several strains of mice (including BALB/c, DBA/2, NOD, C3H and B6 mice) were chosen as donors to construct a memory model of heterotopic cardiac transplantation. The higher degree of MHC mismatch to sensitizing MHC resulted in longer Median survival times (MSTs, BALB/c 3.63 days VS C3H 6.08 days). 3.5 days after cardiac transplantation, compared with the BALB/c and DBA/2 groups, in the groups of NOD and C3H, the infiltration of inflammatory cells in the grafts, the proportion and proliferation of memory cells in spleens, and the function of allogeneic antibodies decreased significantly. The varying degrees of MHC mismatch between the primary and secondary donors influenced the intensity of alloreactive memory cell function, the higher degree of MHC mismatch resulted in better tolerance during secondary transplantation, and these may be related to the changed activation, proliferation and function of the alloreactive memory cells.
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| 5. |
- Xia, Junjie, et al.
(författare)
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Suppressing memory T cell activation induces islet allograft tolerance in alloantigen-primed mice
- 2010
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 23:11, s. 1154-1163
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Tidskriftsartikel (refereegranskat)abstract
- P>Memory T cells are known to play a key role in prevention of allograft tolerance in alloantigen-primed mice. Here, we used an adoptively transferred memory T cell model and an alloantigen-primed model to evaluate the abilities of different combinations of monoclonal antibodies (mAb) to block key signaling pathways involved in activation of effector and memory T cells. In the adoptively transferred model, the use of anti-CD134L mAb effectively prevented activation of CD4+ memory T cells and significantly prolonged islet survival, similar to the action of anti-CD122 mAb to CD8+ memory T cells. In the alloantigen-primed model, use of anti-CD134L and anti-CD122 mAbs in addition to co-stimulatory blockade with anti-CD154 and anti-LFA-1 prolonged secondary allograft survival and significantly reduced the proportion of memory T cells; meanwhile, this combination therapy increased the proportion of regulatory T cells (Tregs) in the spleen, inhibited lymphocyte infiltration in the graft, and suppressed alloresponse of recipient splenic T cells. However, we also detected high levels of alloantibodies in the serum which caused high levels of damage to the allogeneic spleen cells. Our results suggest that combination of four mAbs can significantly suppress the function of memory T cells and prolong allograft survival in alloantigen primed animals.
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