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Allo‐specific T‐Cells Encoding for Viral IL‐10 Exert Strong Immunomodulatory Effects in vitro but Fail to Prevent Graft Rejection
Author(s) -
Brandt Christine,
Yang Jun,
SchmittKnosalla Isabella,
Siepert Anja,
Hammer Markus H.,
Vogt Katrin,
Sawitzki Birgit,
Lehmann Manfred,
Volk HansDieter,
Ritter Thomas
Publication year - 2005
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.1600-6143.2005.00689.x
Subject(s) - transgene , in vitro , in vivo , immune system , immunology , t cell , transplantation , genetically modified mouse , medicine , cancer research , biology , microbiology and biotechnology , gene , genetics , surgery
Recently, we demonstrated the capacity of allo‐specific gene‐engineered T lymphocytes as transport vehicle for therapeutic transgenes into allografts. In this study, the influence of viral IL‐10 as therapeutic transgene was addressed. Lewis rat T‐cell lines specific for DA rat alloantigens were engineered to express vIL‐10 by using a retroviral gene expression system. Like T regulatory 1 cells, vIL‐10 transgenic T lymphocytes express the phenotype CD4 + 25 + and secrete, in addition to vIL‐10, rat IL‐10 and IFN‐γ but no IL‐4. First, the capacity of vIL‐10 transgenic T‐cell lines to modulate alloantigen‐specific immune responses was evaluated in vitro . In comparison to control MLR with no transgenic cells or equal numbers of control T EGFP ‐lymphocytes, the proliferation as well as production of IFN‐γ by naive responder cells were significantly diminished. Despite this regulatory capacity in vitro , T vIL‐10 ‐lymphocytes were not able, either alone or in combination with suboptimal doses of Cyclosporine A, to prolong the survival of either DA rat cardiac or renal allografts in Lewis rat recipients. These data demonstrate that intra‐graft IL‐10 over‐expression is not sufficient to prolong allograft survival in a high‐responder strain combination and that the regulatory capacity of T cells in vitro does not predict their in vivo efficiency.