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

Autor: Brian H. Foresman, R A Sidner, Kathleen M. Heidler, Kena Woods, Carol T. Schnizlein-Bick, Kemba Baker, Oscar W. Cummings, David S. Wilkes
Rok vydání: 2000
Předmět:
Zdroj: American Journal of Respiratory Cell and Molecular Biology. 23:499-505
ISSN: 1535-4989
1044-1549
DOI: 10.1165/ajrcmb.23.4.4172
Popis: 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.
Databáze: OpenAIRE