ABSTRACT
In this study, we investigated interleukin (IL)-18 and IL-12 following in vitro stimulation with either the 30-kDa or purified protein derivative (PPD) antigens (Ag) of pleural mononuclear cells from 12 cases of tubercular pleurisy (TB-PMC) and 8 cases of malignant pleurisy (MG-PMC). Ag-stimulated TB-PMC produced significantly more IL-12 than did MG-PMC and the levels correlated with those of IFN - gamma. Although elevated IL-18 levels were found in freshly isolated pleural fluids, in vitro IL-18 production in response to either Ag was dramatically decreased in TB-PMC. Pro-IL-18 mRNA was detected before and after Ag stimulation in TB patients. Supernatants from the Ag-stimulated TB-PMC significantly suppressed IL-18 production in normal peripheral blood mononuclear cells (PBMC) and primary malignant cells over an 18 h incubation period. In addition, this suppressive activity was not inactivated by either heat or trypsin. Our findings imply that modulation of IL-12 and IL-18 levels may contribute to the Th1 elevation induced in human TB-P VIC by the 30-kDa and PPD antigens.
Subject(s)
Humans , Hot Temperature , Interleukin-12 , Interleukin-18 , Interleukins , Mycobacterium tuberculosis , Pleurisy , RNA, Messenger , Trypsin , Tuberculosis, PleuralABSTRACT
Mycobacterium tuberculosis infected macrophages can become ineffective at activating CD4+ T cells through presentation of peptide antigens by MHC class II, possibly contributing to the ability of M tuberculosis to persist despite the presence of an intact immune system. Presentation of lipid antigens may help to overcome this problem. CD1 represents the key component of an MHC independent pathway for presentation nonpeptide lipid antigens to T cells. The 38 kDa glycolipoprotein antigen of M. tuberculosis is actively secreted. The antigen induces strong antibody and T-cell responses and provided partial protection against M. tuberculosis infection in mice when it is administered either entrapped in biodegradable microparticles or in the form of a DNA vaccine. But an selective anergy to stimulation with peptide of the 38 kDa was observed in the majority of tuberculosis patients. An 38 kDa antigen has been isolated by affinity chromatography using a monoclonal antibody. This antigen contains some immunosuppressive cell wall associated antigens such as lipoarabinomannan. Therefore, we purified the 38 kDa glycolipoprotein from the culture filtrate of M tuberculosis H37Rv by ammonium sulfate precipitation (55~80%), hydroxylapatite and DEAE-Sephacel column. The purified antigen showed three major bands on isoelectric focusing gel, and two-dimensional electrophoresis (2-DE) analysis of this antigen revealed five distinct spots of the 38 kDa molecular mass. One of five spots had a N-terminal sequence identical to that of the 38 kDa glycolipoprotein (pstS-1). Other protein spots could not determine sequences. An antiserum against the recombinant 38 kDa antigen of M tuberculosis reacted strongly with the purified the 38 kDa antigen.
Subject(s)
Animals , Humans , Mice , Ammonium Sulfate , Cell Wall , Chromatography, Affinity , DNA , Durapatite , Electrophoresis , Immune System , Isoelectric Focusing , Macrophages , Mycobacterium tuberculosis , Mycobacterium , T-Lymphocytes , TuberculosisABSTRACT
No abstract available.
Subject(s)
Humans , Interleukin-12 , Mycobacterium tuberculosis , Mycobacterium , Tuberculosis, Pulmonary , Tumor Necrosis Factor-alphaABSTRACT
No Abstract Available.
Subject(s)
Humans , Interleukin-12 , Interleukin-18 , Tuberculosis, PleuralABSTRACT
No Abstract Available.