SECRETION OF THE EOSINOPHIL-ACTIVE CYTOKINES INTERLEUKIN-5, GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-3 BY BRONCHOALVEOLAR LAVAGE CD4(+) AND CD8(+) T-CELL LINES IN ATOPICS ASTHMATICS, AND ATOPIC AND NONATOPIC CONTROLS/

Specific eosinophil accumulation and activation within the asthmatic b ronchial mucosa are thought to occur at least partly through the actio ns of cytokines, including interleukin (TL)-5, IL-3 and granulocyte/ma crophage colony-stimulating factor (GM-CSF). Although mRNA encoding so me of these cytokines has been demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies from asthmatics, it has yet t o be established whether these cells produce the translated products a nd whether expression is associated with CD4(+) T helper or CD8(+) cyt otoxic T cells. We addressed this problem by raising polyclonal CD4(+) and CD8(+) T cell lines from the BAL fluid of six atopic asthmatics, five atopic non-asthmatics and seven non-atopic non-asthmatic controls . BAL fluid cells obtained at fiberoptic bronchoscopy were depleted of adherent cells, and then T lymphocytes expanded by stimulation with m onoclonal anti-CD3 antibody and recombinant human IL-2. When lymphocyt es had expanded to sufficient numbers, CD4(+) and CD8(+) cells were se parated by positive selection with magnetic beads coated with anti-CD4 or anti-CD8 monoclonal antibodies and further expanded. Cytokine secr etion by standardized cell numbers was measured by enzyme-linked immun osorbent assays. BAL CD4(+) T cell lines from the asthmatics secreted significantly elevated quantities of both IL-5 and GM-CSF as compared with lines from the atopic and non-atopic controls (p = 0.023-0.003). In contrast, IL-3 secretion did not significantly differ between the g roups. In some subjects, CD8(+) T cell lines also secreted significant quantities of these cytokines and there was a trend for IL-5 secretio n by these cells to be higher in asthmatics than non-atopic controls ( p = 0.035). These data are consistent with the hypothesis that activat ed T lymphocytes from asthmatics, particularly of the CD4(+) subset, a re predisposed to release elevated quantities of cytokines relevant to the accumulation and activation of eosinophils.