BACKGROUND: T-cell response to alloantigen is dependent on T-cell receptor activation and costimulation through the @entity24083 receptor, because T-cell receptor activation alone is insufficient for optimal immune response. The @entity24083 receptor on helper T cells interacts with its ligand B7 on activated B cells-macrophages as costimulus to support T-cell activity. @entity24084 Ig is a recombinant inhibitor of @entity24083 receptor activation. In vivo studies with a @entity35 major histocompatibility complex mismatch heterotopic cardiac transplant model demonstrate that @entity24084 Ig prolongs cardiac allograft survival. This @entity24084 Ig survival benefit is enhanced with prior donor-specific antigen exposure. METHODS: To investigate @entity24084 Ig mechanisms, we examined the differential expression of B7 and cytokine mRNAs for @entity3692 ( @entity3692 ), @entity5041 ( @entity5041 ), @entity12718 , and @entity13358 (Th1 or Th2 activation) in cardiac allografts after treatment with CTLA4Ig and donor-specific antigen exposure versus conventional immunotherapy ( @entity205 , @entity786 , 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. RESULTS: Inhibition of B7 expression was observed in @entity24084 Ig animals. Expression of @entity5041 and @entity3692 was near undetectable in @entity24084 Ig and @entity786 @entity35 but was only moderately reduced by @entity205 and antilymphocyte serum. @entity12718 mRNA expression was reduced equally in all animals. Finally, @entity13358 levels were unchanged by CTLA4Ig but were decreased by other therapies. CONCLUSIONS: The beneficial effect of CTLA4Ig, inhibiting expression of B7, alters Th1 cytokines @entity5041 and @entity3692 , with a resultant predominant @entity13358 driven, Th2 tolerogenic response.

XXXX blockade alters cytokine mRNA profiles in cardiac transplantation.

@entity3692 :: ('25712(Tax:10116)', 'Gene') :: ['IFN-gamma', 'interferon-gamma'] @entity24084 :: ('63835(Tax:10116)', 'Gene') :: ['CTLA4'] @entity12718 :: ('287287(Tax:10116)', 'Gene') :: ['IL-4'] @entity13358 :: ('25325(Tax:10116)', 'Gene') :: ['IL-10'] @entity786 :: ('MESH:D003520', 'Chemical') :: ['cyclophosphamide'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporine'] @entity5041 :: ('116562(Tax:10116)', 'Gene') :: ['IL-2', 'interleukin-2'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity24083 :: ('25660(Tax:10116)', 'Gene') :: ['CD28']
@entity24083 :: (25660(Tax:10116),Gene) :: ['CD28']
