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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 4, October, 2000 499-505

Instillation of Allogeneic Lung Antigen-Presenting Cells Deficient in Expression of Major Histocompatibility Complex Class I or II Antigens Have Differential Effects on Local Cellular and Humoral Immunity and on Pathology in Recipient Murine Lungs

Kathleen M. Heidler, Kemba Baker, Kena Woods, Carol Schnizlein-Bick, Oscar W. Cummings, Richard Sidner, Brian Foresman, and David S. Wilkes

Departments of Medicine, Microbiology and Immunology, Pathology, and Surgery, Indiana University School of Medicine, Indianapolis, Indiana

Recognition of allogeneic major histocompatibility complex (MHC) molecules expressed on donor lung antigen-presenting cells (APCs) by host T lymphocytes is believed to stimulate lung allograft rejection. However, the specific roles of donor MHC molecules in the rejection response is unknown. We report a murine model in which instilling allogeneic lung APCs into recipient lungs induces pathology analogous to acute rejection, and the production of interferon (IFN)-gamma , immunoglobulin (Ig) G2a, and alloantibodies in recipient lungs. Using allogeneic lung APCs (C57BL/6, I-ab, H-2b) deficient in MHC class I, II, or both for instillation into lungs of BALB/c mice (I-ad, H-2d), the purpose of the current study was to determine the specific roles of donor MHC molecules in stimulating local alloimmune responses. The data show that MHC class I or II on donor APCs induced IFN-gamma and IgG2a synthesis locally, though less than that induced by wild-type cells. Both MHC class I and II were required to induce alloantibody production. Instillation of wild-type or class I- or class II-deficient APCs induced comparable pathologic lesions in recipient lungs, and more severe than that induced by MHC-deficient cells. These data show that donor MHC class I and II molecules have differential effects in the stimulation of local alloimmune responses.




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[Abstract] [Full Text] [PDF]


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