期刊
JOURNAL OF IMMUNOLOGY
卷 169, 期 3, 页码 1168-1174出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.169.3.1168
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- NIAID NIH HHS [P01-AI-41521, AI-33704, R01 AI43578-01] Funding Source: Medline
- NIDDK NIH HHS [DK-10023] Funding Source: Medline
The role of immune response to tissue-specific Ags in transplant rejection is poorly defined. We have previously reported that transplantation of cardiac allografts triggers a CD4(+) Th1 cell response to cardiac myosin (CM), a major contractile protein of the heart, and that pretransplant activation of proinflammatory CM-specific T cells accelerates rejection. In this study, we show that administration of CM together with IFA (CM/IFA) can prevent acute rejection of an allogeneic heart transplant. Prolongation of cardiac graft survival is associated with activation of CM- and allo-specific T cells secreting type 2 cytokines (IL-4, IL-5) and reduction of the frequency of proinflammatory IFN-gamma-secreting (type 1) alloreactive T cells. Blocking of IL-4 cytokine with Abs abrogates the prolongation. CM/IFA treatment prevents acute rejection of MHC class 1-mismatched, but not fully mismatched grafts. However, if donor heart is devoid of MHC class 11 expression, CM-IFA administration delays rejection of fully allogeneic cardiac transplants. This finding suggests that the effect of CM modulation depends on the type (direct vs indirect) and strength of recipient's CD4(+) T cell alloresponse. Our results underscore the important role of host immunity to tissue-specific Ags in the rejection of an allograft. This study demonstrates that modulation of the immume response to a tissue-specific Ag can significantly prolong cardiac allograft survival, an observation that may have important implications for the development or novel selective immune therapies in transplantation.
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