| 1. |
|
|
| 2. |
- Dai, Helong, et al.
(författare)
-
Blockade of CD27/CD70 pathway to reduce the generation of memory T cells and markedly prolong the survival of heart allografts in presensitized mice
- 2011
-
Ingår i: Transplant Immunology. - : Elsevier BV. - 1878-5492 .- 0966-3274. ; 24:4, s. 195-202
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alloreactive memory T cells are a major obstacle to transplantation acceptance due to their capacity for accelerated rejection. Methods: C57BL/6 mice that had rejected BALB/c skin grafts 4 weeks earlier were used as recipients. The recipient mice were treated with anti-CD154/LFA-1 with or without anti-CD70 during the primary skin transplantation and anti-CD154/LFA-1 or not during the secondary transplantation of BALB/c heart. We evaluated the impact of combinations of antibody-mediated blockade on the generation of memory T cells and graft survival after fully MHC-mismatched transplantations. Results: One month after the primary skin transplantation, the proportions of CD4(+) memory T cells/CD4(+) T cells and CD8(+)memory T cells/CD8(+) T cells in the anti-CD154/LFA-1 combination group were 47.32 +/- 428% and 23.18 +/- 2.77%, respectively. In the group that included anti-CD70 treatment, the proportions were reduced to 34.10 +/- 2.71% and 12.19 +/- 3.52% (P<0.05 when comparing the proportion of memory T cells between the two groups). The addition of anti-CD70 to the treatment regimen prolonged the mean survival time following secondary heart transplantation from 10 days to more than 90 days (P<0.001). Furthermore, allogenic proliferation of recipient splenic T cells and graft-infiltrating lymphocytes were significantly decreased. Meanwhile, the proportion of regulatory T cells was increased to 9.46 +/- 1.48% on day 100 post-transplantation (P<0.05). Conclusions: The addition of anti-CD70 to the anti-CD154/LFA-1 combination given during the primary transplantation reduced the generation of memory T cells. This therapy regimen provided a potential means to alleviate the accelerated rejection mediated by memory T cells during secondary heart transplantation and markedly prolong the survival of heart allografts. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 3. |
- Kang, Xiangpeng, et al.
(författare)
-
Isatis tinctoria L. combined with co-stimulatory molecules blockade prolongs survival of cardiac allografts in alloantigen-primed mice
- 2010
-
Ingår i: Transplant Immunology. - : Elsevier BV. - 1878-5492 .- 0966-3274. ; 23:1-2, s. 34-39
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 4. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 5. |
- Wang, Feng, et al.
(författare)
-
The major histocompatibility complex (MHC) of the secondary transplant tissue donor influences the cross-reactivity of alloreactive memory cells.
- 2011
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 73, s. 190-197
-
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.
|
|
