T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis

Andersen, Peter; Askgaard, Dorthe; Ljungqvist, L; Bentzon, Michael Weis; Heron, Iver

doi:10.1128/iai.59.4.1558-1563.1991

Cited by 169 publications

(104 citation statements)

References 27 publications

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“…To date, only a few immunogenic proteins have been identi-¢ed and characterized [1]. Of particular interest are the secreted proteins, which have been implicated as protective antigens in M. tuberculosis infections [4]. Secreted proteins have not been studied extensively in M. paratuberculosis because of the high concentration of bovine serum albumin required to sustain bacterial growth in vitro, which hinders the identi¢cation and separation of these proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Superoxide dismutases (Sods; EC 1.15.1.1) catalyze the dismutation of superoxide radicals into hydrogen peroxide and molecular oxygen, and may protect M. paratuberculosis against oxidative stress. A secreted Sod has been identi¢ed as a predominant protein in culture supernatant £uids of Mycobacterium tuberculosis [4]. Furthermore, Sod is secreted in signi¢cantly higher proportions by pathogenic M. tuberculosis than non-pathogenic Mycobacterium smegmatis [6].…”

Section: Introductionmentioning

confidence: 99%

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Identification of a secreted superoxide dismutase in Mycobacterium avium ssp. paratuberculosis

Liu

2001

FEMS Microbiology Letters

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Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis), the causative agent of Johne's disease, is an important animal pathogen that has also been implicated in human disease. The major proteins expressed by M. paratuberculosis were analyzed by two-dimensional gel electrophoresis, and a superoxide dismutase (Sod) was identified from this protein profile. The M. paratuberculosis Sod has a molecular mass of 23 kDa and an isoelectric point of 6.1. Sequence analysis of the corresponding sodA gene from M. paratuberculosis indicates that this protein is a manganese-dependent enzyme. We show that the M. paratuberculosis Sod is actively secreted, suggesting that it may elicit a protective cellular immune response in the host during infection. ß

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a secreted superoxide dismutase in Mycobacterium avium ssp. paratuberculosis

Liu

2001

FEMS Microbiology Letters

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“…Purified native (n) MPB64 stimulates T cell responses in Myco. tuberculosis-infected mice [5] and in human TB patients [6]. Furthermore, nMPB64 is capable of eliciting DTH reactions in Myco.…”

Section: Introductionmentioning

confidence: 99%

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Roche

Winter

Triccas

et al. 1996

Clinical and Experimental Immunology

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SUMMARYProteins secreted across the cell wall of mycobacteria are important antigens recognized early in the host response to mycobacterial infection. MPT64 is a 23-kD secreted protein restricted to members of the Mycobacterium tuberculosis complex which elicits T cell responses and cutaneous DTH reactions in Myco. tuberculosis-infected animals. Patients with tuberculosis and their tuberculin-positive contacts respond to the protein, but recipients of bacille Calmette-Guérin (BCG) vaccine strains lacking the mpt64 gene do not. In the present study, we describe the development of a unique recombinant mycobacterial vector which secretes the encoded Myco. tuberculosis protein MPT64 at high levels into the culture filtrate, from which the protein is isolated by a single-step affinity chromatographic step. The purified protein was recognized by both polyclonal and monoclonal anti-MPT64 antibodies. The T cell reactivity of the protein was confirmed by its ability to stimulate human anti-rMPB64 T cell lines. The Myco. smegmatis recombinant MPT64 protein was superior to the Escherichia coli rMPB64 protein, which has identical amino acid sequence, in eliciting cutaneous DTH reactions in guinea pigs sensitized with Myco. tuberculosis. Animals sensitized with BCG strains lacking the mpb64 gene failed to respond to MPT64. Similarly, interferon-gamma (IFN-) responses in tuberculosis patients and their contacts were higher to the Myco. smegmatis form of the protein. The potential of this form of the Myco. tuberculosis MPT64 protein as a skin test reagent for tuberculosis is discussed.

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“…ST-CF was produced at the Statens Seruminstitut (Copenhagen, Denmark) as described previously. 19 Brie¯y, M. tuberculosis (4r10 6 colony-forming units (CFU)/ml) was grown in modi®ed Sauton medium without Tween-80 on an orbital shaker for 7 days. The culture supernatants were sterile ®ltered and concentrated on an Amicon YM3 membrane (Amicon, Danvers, MA).…”

Section: Reagentsmentioning

confidence: 99%

Interleukin‐6 regulates the phenotype of the immune response to a tuberculosis subunit vaccine

et al. 2001

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Summary We investigated the role of interleukin‐6 (IL‐6) in the development of the immune response to a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis emulsified in the adjuvant dimethyldioctadecylammonium bromide (DDA). C57Bl/6 mice immunized with this vaccine developed a strong T helper 1 (Th1) response characterized by an increased production of interferon‐γ (IFN‐γ) secreted by CD4+ T cells. Neutralization of IL‐6 during in vivo priming resulted in marked reduction in the ability of T cells to secrete IFN‐γ and IL‐2 and to proliferate. IL‐6 gene‐disrupted mice primed with the vaccine showed a decrease in the number of IFN‐γ‐producing cells and an increase in IL‐4‐secreting cells as compared to control mice. In contrast, neutralization of IL‐6 during a boost of the vaccine in previously primed mice did not affect the development of IFN‐γ‐producing cells but still increased the number of IL‐4‐producing cells. Our work shows that IL‐6 plays a major role in the priming but not in the later expression of a Th1 response to a tuberculosis vaccine.

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T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis

Cited by 169 publications

References 27 publications

Identification of a secreted superoxide dismutase in Mycobacterium avium ssp. paratuberculosis

Identification of a secreted superoxide dismutase in Mycobacterium avium ssp. paratuberculosis

Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis: purification, immunogenicity and application to skin tests for tuberculosis

Interleukin‐6 regulates the phenotype of the immune response to a tuberculosis subunit vaccine

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