Lysis of pulmonary fibroblasts by lymphokine (IL-2)-activated killer cells--a mechanism affecting the human lung microenvironment?
In this study we investigated whether IL-2-activated killer cells may bind and exert lytic activity against non-transformed lung fibroblasts. We demonstrated that human lymphokine-activated killer (LAK) cells generated in vitro following incubation with recombinant IL-2 of either peripheral blood mononuclear cells (PB-LAK) or lymphocytes obtained from bronchoalveolar lavage (BAL-LAK), but not resting cells, can lyse normal lung fibroblasts obtained from transbronchial lung biopsies in a 4-h 51Cr release assay. Both autologous and allogeneic fibroblasts were consistently lysed by LAK cells, thus suggesting that the phenomenon we observed is not MHC-restricted. Since fibroblasts can bind IL-2 through specific receptors, we evaluated whether long-term culture with rIL-2 could modulate the susceptibility to lysis of target cells. Our data showed that autologous fibroblasts were more resistant to lysis than allogeneic fibroblasts when they were cultured with rIL-2. Since LAK cells have been demonstrated to release a series of different immunomodulatory cytokines, we evaluated the effect of short-term incubation of fibroblasts with different factors, including IL-1, IL-2, IL-3, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), on the binding and the lysis mediated by LAK cells. These cytokines were not directly cytotoxic on fibroblasts. Only IFN-gamma was found to have a significant protective effect against the lysis. Our data support the concept that a self-directed cytotoxicity against pulmonary fibroblasts is generated during lymphocyte activation with rIL-2.
Zambello
R
R
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Italy.
Trentin
L
L
Enthammer
C
C
Cipriani
A
A
Agostini
C
C
Semenzato
G
G
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2