Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs.
Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs.
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DOI：
10.4049/jimmunol.1200870
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Smyth LA;Ratnasothy K;Moreau A;Alcock S;Sagoo P;Meader L;Tanriver Y;Buckland M;Lechler R;Lombardi G
Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in-vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but accelerated graft rejection. The latter was inhibited by recipient injection with anti-CD8 antibody, which removed both CD8+ T cells and CD8+ DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC-alloantigens by recipient antigen presenting cells (APCs) and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using T cell receptor-transgenic T cells, antigen presentation of injected OVA-pulsed DCs was detectable for ≤3 days whilst indirect presentation of MHC alloantigen by recipient APCs led to activation of T cells within 14 hours and was partially inhibited by reducing the numbers of CD8+ DCs in vivo. In support of this observation when mice lacking CD8+ DCs were pretreated with drug-modified DCs prior to transplantation, skin graft rejection kinetics were similar to non-DC treated controls. Interestingly, when the same mice were treated with anti-CD40L blockade plus drug-modified-DCs skin graft survival was prolonged, suggesting endogenous DCs were responsible for T cell priming. Altogether, these findings highlight the risks and limitations of negative vaccination using alloantigen bearing “tolerogenic” DCs.
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DOI：
10.1006/bbrc.2000.2490
发表时间：
2000-04-21
影响因子：
3.1
作者：
Griffin, MD;Lutz, WH;Kumar, R
通讯作者：
Kumar, R
影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
8.8
作者：
Buckland, M.;Jago, C. B.;Lombardi, G.
通讯作者：
Lombardi, G.
影响因子：
20.3
作者：
Fonteneau, JF;Kavanagh, DG;Larsson, M
通讯作者：
Larsson, M
影响因子：
4.4
作者：
Bonham, CA;Peng, LS;Lu, L
通讯作者：
Lu, L