Characterization of Normal Human Lung Lymphocytes and Interleukin-2-induced Lung T Cell Lines

Lymphocytes from the lower respiratory tract were obtained by bronchoalveolar lavage of healthy, non-smoking individuals. Various monoclonal antibodies characterizing activated T cells, helper-inducer and suppressor-inducer T cell subsets, and naive versus memory cells were used to define the phenotype of these lymphocytes. The highly variable CD4/CD8 ratio (0.3 to 6.6; mean = 2.1) and the large proportion of the T cells expressing HLA-DR (9 to 38%; mean = 21%) suggested that the T cells were recently activated by antigens selectively stimulating either helper or cytotoxic/suppressor T cell function. Indeed, the CD45RA antigen, a marker characteristic of suppressor-inducer T cells when coexpressed with CD4, and naive T cells in general, was absent from T cells in most preparations (0 to 17%; mean = 5%), while the CD45RO antigen, a marker of memory cells and immature thymocytes, was present on 68 to 100% of all lung T cells. The majority (> 70%) of the CD4+ helper T cells was CD45RO+ CD45RA−, a phenotype found on T cells that provide help for B cell immunoglobulin synthesis. Lung T cells proliferated poorly in response to phytohemagglutinin and concanavalin A but did respond to activation with low concentrations of anti-CD3 mAb (2 to 25 ng/ml) and to interleukin-2 (IL-2) alone to similar extent as did autologous peripheral blood lymphocytes. Stimulation of lung T cells having a CD4/CD8 ratio of > 2 with IL-2 (100 U/ml) resulted in outgrowth of helper T cell lines (CD2, CD3, CD4, TCRα/β, CD45RO) with no cytotoxic activity against K562 tumor target cells. In contrast, stimulation of cell preparations with a CD4/CD8 ratio < 2 resulted in T cell lines with low cytotoxic activity against K562 cells. These latter lines contained > 40% CD8+ cells, all of which expressed the TCRα/β. Cytotoxic activity did not correlate with expression of natural killer (NK) antigen CD56 (Leu19). Helper cell lines were maintained for at least 3 mo in culture, while cytotoxic cell lines proliferated for < 6 wk. These data show that the lower respiratory tract of humans contains immunocompetent lymphocytes that may have been recently activated and are long-lived memory cells of either the helper or the cytotoxic/suppressor cell type, both of which are capable of proliferation in response to appropriate stimulation (anti-CD3 mAb or IL-2).