Am. J. Respir. Cell Mol. Biol., Volume 23, Number 1, July, 2000 62-70

Type V Collagen Modulates Alloantigen-Induced Pathology and Immunology in the Lung

David C. Mares, Kathleen M. Heidler, Gerald N. Smith Jr., Oscar W. Cummings, Erinn R. Harris, Brian Foresman, and David S. Wilkes

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

Perivascular and peribronchiolar tissues are targets of the immune response during lung allograft rejection. Collagen type V (col[V]) is located within these tissues. Col(V) may be major histocompatibility complex (MHC)-like, and MHC-derived peptides have been used to induce immunologic tolerance and prevent rejection in allografts other than the lung. The current study tests the hypothesis that col(V) could be used to downregulate immune responses to lung alloantigen in vivo. We developed a murine model in which instillations of allogeneic bronchoalveolar lavage (BAL) cells (C57BL/6, I-a^b, H-2^b) into lungs of BALB/c mice (I-a^d, H-2^d) induce histology similar to grades 1 and 2 acute lung allograft rejection, apoptosis of airway epithelium and vascular endothelium, and upregulate tumor necrosis factor (TNF)- production locally. The current study reports that instillations of col(V) into lungs before allogeneic BAL cells prevent development of rejection pathology and apoptosis, downregulate alloantigen-induced T-lymphocyte proliferation, and abrogate local TNF- production. In addition, instillation of col(V)-pulsed autologous BAL cells into lungs of mice primed with allogeneic BAL cells perpetuates rejection pathology. Collectively, these data show that col(V) is a novel antigen involved in the rejection process, and suggest that col(V) could be used to modulate the rejection response to lung allografts.

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