Limiting-dilution analysis of T cells extracted from solid human lung tissue: comparison of precursor frequencies for proliferative responses and lymphokine production between lung and blood T cells from individual donors.

This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal human lung yielded 18-42 x 10(6) viable mononuclear cells per gram wet weight tissue, of which 60-72% were lymphocytes; based upon these recoveries and the known weight of adult lung, the (median) lung parenchymal lymphocyte population can be estimated as 6 x 10(9), being of the same order as the blood pool and 15-30-fold that recoverable by broncho-alveolar lavage. Flow cytometric analysis indicated that the bulk of these lymphocytes was OKT3+/T11+ (CD3/CD2) T cells. Purified blood and lung T cells from each subject were cultured at limiting dilution in the presence of PHA, irradiated feeder cells and recombinant human IL-2. The mean frequency estimates for PHA-responsive T cells in these populations were 1 in 1.23 (81%) and 1 in 3.22 (31%) for blood and lung, respectively. This difference was seen for T cells from each donor and was highly significant by paired t-test (P less than 0.002). Analysis of surface phenotypes and functions of individual blood and T-cell clones indicated comparable frequencies for OKT4 (CD4) and OKT8 (CD8) expression, TNF production and mitogen-induced cytotoxicity. However, a striking inverse relationship was observed between the overall frequency of IL-2-producing clones (79% for blood versus 47% for lung) and interferon-gamma (IFN-gamma)-producing clones (46% versus 87%). These differences were found for each subject, and both were highly significant (P less than 0.001) by paired t-test. The available literature suggests that the majority of these lung T cells represent transient immigrants derived from the blood. Accordingly, the functional differences we have observed suggest either selective trapping within the lung vascular bed of peripheral blood T cells of certain functional phenotypes or alternatively selection/modulation of T cells by lung-derived factors during their transit through the tissue.