Mycobacterial‐induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients

Kaleab, Birhane; Ottenoff, Tom; Converse, Paul J.; Halapi, Eva; Tadesse, Genet; Rottenberg, Martı́n E.; Kiessling, Rolf

doi:10.1002/eji.1830201219

Cited by 88 publications

(48 citation statements)

References 31 publications

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“…The NK cells exhibit non-MHC restricted cytotoxic activity, as recently demonstrated with macrophages infected with live BCG [94] or M. tuberculosis [95]. Activity of NK cells could be generated from lymphocytes of human TB and leprosy patients upon stimulation with mycobacterial antigens [77,[96][97][98]. The major importance of this subset may be as a source of IFN-g early during infection.…”

Section: Host Responses and Antigens Involved In Protective Immunity mentioning

confidence: 97%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Andersen P. Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis. Scand J Immunol 1997;45:115-131 Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

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Section: Host Responses and Antigens Involved In Protective Immunity mentioning

confidence: 97%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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“…ϩ and CD4 ϩ T cells can function as class I-and class II-restricted cytotoxic T cells, respectively, and both are capable of lysing M. leprae-infected M (65,149,192). Lysis of target cells by cytotoxic T lymphocytes is mediated by perforin and cytotoxic granules such as granzyme B, a serine protease located in cytotoxic T cells and NK cells (369).…”

Section: (Iii) Cytotoxic Cells (A) T Cells Cd8mentioning

confidence: 99%

The Continuing Challenges of Leprosy

et al. 2006

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SUMMARY Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

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“…ϩ T cells has been demonstrated (10,11), but very little is known about which Ags are recognized by such T cells. Only two mycobacterial epitopes that are recognized by HLA class I-restricted CD8 ϩ T cells have been reported: an HLA-B52-restricted epitope of M. tuberculosis and an HLA-A*0201-restricted peptide of the 19-kDa lipoprotein (13).…”

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confidence: 99%

Identification of Major Epitopes ofMycobacterium tuberculosisAG85B That Are Recognized by HLA-A*0201-Restricted CD8+ T Cells in HLA-Transgenic Mice and Humans

Geluk

Meijgaarden

Franken

et al. 2000

The Journal of Immunology

144

111

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CD8+ T cells are thought to play an important role in protective immunity to tuberculosis. Although several nonprotein ligands have been identified for CD1-restricted CD8+ CTLs, epitopes for classical MHC class I-restricted CD8+ T cells, which most likely represent a majority among CD8+ T cells, have remained ill defined. HLA-A*0201 is one of the most prevalent class I alleles, with a frequency of over 30% in most populations. HLA-A2/Kb transgenic mice were shown to provide a powerful model for studying induction of HLA-A*0201-restricted immune responses in vivo. The Ag85 complex, a major component of secreted Mycobacterium tuberculosis proteins, induces strong CD4+ T cell responses in M. tuberculosis-infected individuals, and protection against tuberculosis in Ag85-DNA-immunized animals. In this study, we demonstrate the presence of HLA class I-restricted, CD8+ T cells against Ag85B of M. tuberculosis in HLA-A2/Kb transgenic mice and HLA-A*0201+ humans. Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8+ CTLs were identified. These CD8+ T cells produced IFN-γ and TNF-α and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages. This CTL-mediated killing was blocked by anti-CD8 or anti-HLA class I mAb. Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8+ T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201+ individuals. Collectively, our results demonstrate the presence of HLA class I-restricted CD8+ CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8+ T cells in humans and mice. These epitopes thus represent potential subunit components for the design of vaccines against tuberculosis.

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Mycobacterial‐induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients

Cited by 88 publications

References 31 publications

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

The Continuing Challenges of Leprosy

Identification of Major Epitopes ofMycobacterium tuberculosisAG85B That Are Recognized by HLA-A*0201-Restricted CD8+ T Cells in HLA-Transgenic Mice and Humans

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