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

• Published in: American journal of respiratory cell and molecular biology Vol. 23; no. 4; pp. 499 - 505
• Main Authors: Heidler, Kathleen M, Baker, Kemba, Woods, Kena, Schnizlein-Bick, Carol, Cummings, Oscar W, Sidner, Richard, Foresman, Brian, Wilkes, David S
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.10.2000
• Subjects: Animals; Antigen-Presenting Cells - immunology; Bronchoalveolar Lavage Fluid - cytology; Cell Transplantation; Female; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; Isoantibodies - immunology; Lung - immunology; Lung - pathology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.23.4.4172

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-a(b), H-2(b)) deficient in MHC class I, II, or both for instillation into lungs of BALB/c mice (I-a(d), H-2(d)), 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.