Legionella pneumophila protease inactivates interleukin-2 and cleaves CD4 on human T cells.
The role of the Legionella pneumophila protease in the pathogenesis of Legionnaires' disease is unclear. In this study, we assessed the effect of purified protease preparations on human recombinant interleukin-2 (IL-2), the IL-2 receptor, and several additional human T-cell surface proteins to determine whether protease contributes to the virulence of L. pneumophila by interfering with human T-cell activation and function. IL-2-induced proliferation of CTLL-2 cells was inhibited by coincubation with protease (10 to 100 U/ml). Protease at concentrations of > or = 10 U/ml cleaved human recombinant IL-2 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing 125I-labeled IL-2 and protease. Protease treatment of activated human T cells did not inhibit binding of a monoclonal antibody directed against the alpha subunit of the IL-2 receptor and did not interfere with binding of IL-2 to IL-2 receptors on the lymphocytes. Treatment of blood mononuclear cells or activated T cells with protease (50 U/ml) inhibited the binding of a monoclonal antibody directed against CD4. In contrast, protease treatment did not inhibit the binding of antibodies against CD3, CD8, class II major histocompatibility complex, and the transferrin receptor. Heat inactivation (65 degrees C for 20 min) of the protease or treatment with the metal chelator EDTA ablated the inhibitory effect of the protease. The ability of the protease to degrade IL-2 and cleave CD4 on human T cells suggests that protease may contribute to the pathogenesis of Legionnaires' disease by impeding T-cell activation and immune function.
Mintz
C S
CS
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Miller
R D
RD
Gutgsell
N S
NS
Malek
T
T
D001426:Bacterial Proteins; D015704:CD4 Antigens / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016952:Legionella pneumophila / Q000201:enzymology*; D008213:Lymphocyte Activation; D008666:Metalloendopeptidases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D001426:Bacterial Proteins; D015704:CD4 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa