Phenotypic analysis of pulmonary perivascular mononuclear infiltrates that occur as a direct result of acute lethal graft-versus-host disease describes the onset of interstitial pneumonitis.

We recently determined that the sequential development of interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis occurs as a direct result of acute lethal graft-versus-host disease. Interstitial pneumonitis develops before lymphocytic bronchiolitis/bronchitis primarily from the dissemination of perivascular mononuclear infiltrates. We have used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppression, or overt infection to determine the phenotype of infiltrating perivascular mononuclear cells throughout acute lethal graft-versus-host disease. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Graft-versus-host disease animals were killed on days 3, 7, 10, 14, and 15 to 21 after injection. Whole left lung lobes were frozen, serially sectioned (4 microns), and incubated with a panel of mouse anti-rat monoclonal antibodies. Labeled antibody density was determined by computerized image analysis. Perivascular infiltration was observed first for ED1+, OX8+, and W3/25+ cells, and then OX41+, W3/13+ and OX19/25+ populations. OX6 was expressed in control tissues and at all time points tested. OX12+, OX39+ and MOM/3F12/F2+ cells were not quantifiable. The present study has determined that the process of perivascular infiltration was produced through a biphasic influx of OX6+, T-cell, and macrophage populations.