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Maturation‐Resistant Dendritic Cells Induce Hyporesponsiveness in Alloreactive CD45RA + and CD45RO + T‐Cell Populations
Author(s) -
Woltman A. M.,
Van Der Kooij S. W.,
De Fijter J. W.,
Van Kooten C.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01520.x
Subject(s) - immunology , cd28 , t cell , immune tolerance , microbiology and biotechnology , dendritic cell , medicine , immune system , cytotoxic t cell , biology , in vitro , biochemistry
Dendritic cells (DCs) play a crucial role in the induction of antigen‐specific immunity and tolerance. Considering in vivo application of DCs prior to human organ transplantation, a protocol to develop tolerogenic DCs that not only induce unresponsiveness in naive (CD45RA + ) T cells, but also in alloreactive memory (CD45RO + ) T cells is required. The present study shows that dexamethasone (Dex) alters the differentiation of human monocyte‐derived DCs. DexDCs cocultured with allogeneic CD4 + T cells induced low proliferating and low IFNγ producing T cells. This is caused by lack of both costimulation via CD28 and hampered production of a soluble factor, as well as additional active suppression via B7‐H1 and IL‐10. T cells primed by DexDCs demonstrated hyporesponsiveness upon restimulation with mature DCs seemingly via the induction of anergy, since these cells showed no enhanced apoptosis and only a limited suppressive capacity. Interestingly, not only cocultures of allogeneic CD45RA + , but also of CD45RO + T cells with DexDCs rendered T‐cell populations hyporesponsive to restimulation with mature DCs. The finding that also alloreactive memory T cells can be regulated supports the rationale of cell‐based therapies to obtain allograft‐specific tolerance in transplant recipients.