Open AccessLysis of pulmonary fibroblasts by lymphokine (IL‐2)‐activated killer cells—a mechanism affecting the human lung microenvironment?
Author(s) -
ZAMBELLO R.,
TRENTIN L.,
ENTHAMMER C.,
CIPRIANI A.,
AGOSTINI C.,
SEMENZATO G.
Publication year - 1996
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1996.d01-762.x
Subject(s) - lymphokine activated killer cell , lymphokine , cytotoxic t cell , immunology , bronchoalveolar lavage , interleukin 2 , biology , tumor necrosis factor alpha , cytokine , fibroblast , lymphocyte , cytotoxicity , immune system , microbiology and biotechnology , in vitro , lung , medicine , interleukin 21 , t cell , biochemistry
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 51 Cr 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‐α), and interferon‐gamma (IFN‐γ), on the binding and the lysis mediated by LAK cells. These cytokines were not directly cytotoxic on fibroblasts. Only IFN‐γ 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.