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- W2087638514 abstract "T-cell response to alloantigen is dependent on T-cell receptor activation and costimulation through the CD28 receptor, because T-cell receptor activation alone is insufficient for optimal immune response. The CD28 receptor on helper T cells interacts with its ligand B7 on activated B cells-macrophages as costimulus to support T-cell activity. CTLA4Ig is a recombinant inhibitor of CD28 receptor activation. In vivo studies with a rat major histocompatibility complex mismatch heterotopic cardiac transplant model demonstrate that CTLA4Ig prolongs cardiac allograft survival. This CTLA4Ig survival benefit is enhanced with prior donor-specific antigen exposure.To investigate CTLA4Ig mechanisms, we examined the differential expression of B7 and cytokine mRNAs for interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 (Th1 or Th2 activation) in cardiac allografts after treatment with CTLA4Ig and donor-specific antigen exposure versus conventional immunotherapy (cyclosporine, cyclophosphamide, or antilymphocyte serum). In the above major histocompatibility complex mismatch model, hearts (on day 5 after transplantation at peak rejection) had cytokine mRNA expression determined by semiquantitative reverse transcriptase-polymerase chain reaction.Inhibition of B7 expression was observed in CTLA4Ig animals. Expression of IL-2 and IFN-gamma was near undetectable in CTLA4Ig and cyclophosphamide rats but was only moderately reduced by cyclosporine and antilymphocyte serum. IL-4 mRNA expression was reduced equally in all animals. Finally, IL-10 levels were unchanged by CTLA4Ig but were decreased by other therapies.The beneficial effect of CTLA4Ig, inhibiting expression of B7, alters Th1 cytokines IL-2 and IFN-gamma, with a resultant predominant IL-10 driven, Th2 tolerogenic response." @default.
- W2087638514 created "2016-06-24" @default.
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- W2087638514 date "1997-08-01" @default.
- W2087638514 modified "2023-09-27" @default.
- W2087638514 title "CD28 blockade alters cytokine mRNA profiles in cardiac transplantation" @default.
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- W2087638514 doi "https://doi.org/10.1016/s0039-6060(97)90001-5" @default.
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