Graft-Versus-Host Reaction in the Lung

Studies were initiated to determine if cells migrate across the bronchoalveolar epithelium of the lung into the interstitium. A graft-versus-host reaction (GVHR) was chosen as the assay, to indicate that immunocompetent lymphocytes had reached the interstitium and regional lymph node. Intratracheal inoculation of parental lymph node cells into the airways of the lungs of F1 hybrid hamsters elicited a local GVHR characterized at 7 days by an intense mononuclear infiltration in the alveolar spaces and interstitium and a distinctive accumulation of lymphocytes around the veins and arteries. Regional (hilar) lymph nodes were hypertrophied and a diffuse lymphoid hyperplasia was demonstrated on histological examination. Later a systemic GVHR occurred as evidenced by an increased splenic weight and thymic atrophy. Even though only a small percentage of total radioactivity inoculated as 51Cr-labeled donor lymph node cells was documented in regional nodes at day 7, when hilar lymph node cells were adoptively transferred from F1 hybrids with pulmonary GVHR, a local GVHR was induced in a secondary F1 host. The lungs of F1 hybrid hamsters with systemic GVHR induced by either intracutaneous or i.v. inoculation of parental cells were studied and found to be free of detectable pathological change. These findings suggested that the pulmonary reaction in the locally inoculated animals resulted entirely from the initial contact of inoculated cells with host histocompatibility antigens and recirculating graft-versus-host-reactive cells did not induce the reaction. Since parental lymphocytes inoculated into the lungs of F1 hybrid animals induced a local and later a systemic GVHR, it was concluded that the viable cells introduced into the bronchoalveolar spaces trafficked across the bronchoalveolar epithelium into the lung. Thus, the possibility is raised that a similar migration of endogenous cells occurs across the epithelium. Such traffic of cells between the body and the alveolar spaces could be important in the development of the specific and nonspecific defenses of the lower respiratory tract.