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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Abatacept, Animals, Antigens, CD, Antigens, Differentiation, Antilymphocyte Serum, CD28 Antigens, CTLA-4 Antigen, Cyclophosphamide, Cyclosporine, Cytokines, Graft Survival, Heart Transplantation, Immunoconjugates, Immunosuppressive Agents, Interferon-gamma, Interleukin-10, Interleukin-2, Interleukin-4, Isoantigens, Lymphocyte Activation, Male, Polymerase Chain Reaction, RNA, Messenger, Rats, Rats, Inbred BN, Rats, Inbred Lew, T-Lymphocytes, Th1 Cells, Th2 Cells, Transcription, Genetic, Transplantation, Homologous.
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Does cD28 blockade alter cytokine mRNA profiles in cardiac transplantation? Context: 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.
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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. Final Decision: yes