T lymphocyte responses of murine lung: Immunization with alloantigen induces accumulation of cytotoxic and other T lymphocytes in the lung

Pulmonary T lymphocyte responses were assessed by comparing the cytotoxic activities of lymphocyte populations from pulmonary (bronchoalveolar wash, lung) and other (blood, spleen) sources after intratracheal or intraperitoneal immunization of C57BL/6 mice with allogeneic P815 cells. Based on the distribution of radioactivity after instillation of ⁵¹Cr-P815 cells, antigen remained localized at the site of instillation for at least 2 days. Both routes of immunization induced cytotoxic activity in all cell populations, and the activity was due entirely to cytotoxic T lymphocytes. After intratracheal immunization, cytotoxic activity in lung and spleen appeared by day 7, reached a peak on days 10 to 13, then fell; the ratio of lung:spleen activity was 2:1. However, the magnitude of the response was low and could not be augmented by increasing the immunizing dose. After i.p. immunization, the time course of the cytotoxic response was similar to that after intratracheal immunization, but the magnitude of the response was 5-fold greater. Unexpectedly, i.p. immunization also resulted in a ratio of lung:spleen activity of 2:1. The high lung activity was caused by a higher frequency of CTL in lung than spleen; the efficiency of killing of lung CTL was the same as that of spleen CTL. The high activity in lung was not due to the method of obtaining cells, since treatment of lung with collagenase resulted in a tripling of cell yield but the same level of activity. Maximal cytotoxic responses to i.p. immunization were associated with 1.6-fold increases in cell yields from both lung and spleen. The percentage of T lymphocytes in the spleen did not change with immunization, but the percentage of T lymphocytes in the lung increased from 30 to 52%. Thus, the increase in cell yield from lungs of immune mice was due almost entirely to the nearly 3-fold increase in absolute numbers of T lymphocytes. Specific cytotoxic lymphocytes accounted for 9% or less of lung T lymphocytes and 4% or less of splenic T lymphocytes. The results suggest that after i.p. immunization, the lung is a preferred site of accumulation of CTL and of other T lymphocytes stimulated by the immune response. The T lymphocytes accumulate by a mechanism that is apparently independent of local antigenic stimulation.