CD8 T cells and Mycobacterium tuberculosis infection

Lin, Philana Ling; Flynn, JoAnne L.

doi:10.1007/s00281-015-0490-8

Cited by 185 publications

(152 citation statements)

References 81 publications

(92 reference statements)

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“…However, it appears that the increased CD8 + and CD4 − CD8 − T cells in BAL in the post-exposure boost may at least be partially contributing to increased reduction in Mtb viable counts (Figures 1, 3). For an intracellular pathogen like Mtb, besides cytokine-mediated mechanisms, cytotoxic lymphocytes are expected to play a significant role in removing the infected host cells, thereby clearing the infection (48). Interestingly, BCG vaccine has been known to predominantly induce CD4 + T cells and attempts to broaden the response toward both CD4 + and CD8 + T cell responses have included boosting with recombinant adenovirus vector containing Ag85A and B, and making recombinant BCG more amenable to inducing CD8 + T cell response by including multiple antigens and perfringolysin (49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

et al. 2018

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Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of Mtb emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults. The protective immunity afforded by BCG is thought to wane with time and considered to last only through adolescent years. Heterologous boosting of BCG-primed immune responses using a subunit vaccine represents a promising vaccination approach to promote strong cellular responses against Mtb. In our earlier studies, we discovered lipopeptides of ESAT-6 antigen with strong potential as a subunit vaccine candidate. Here, we have investigated that potential as a booster to BCG vaccine in both a pre-exposure preventive vaccine and a post-exposure therapeutic vaccine setting. Surprisingly, our results demonstrated that boosting BCG with subunit vaccine shortly before Mtb challenge did not improve the BCG-primed immunity, whereas the subunit vaccine boost after Mtb challenge markedly improved the quantity and quality of effector T cell responses and significantly reduced Mtb load in lungs, liver and spleen in mice. These studies suggest that ESAT-6 lipopeptide-based subunit vaccine was ineffective in overcoming the apparent immunomodulation induced by BCG vaccine in Mtb uninfected mice, but upon infection, the subunit vaccine is effective in re-educating the protective immunity against Mtb infection. These important results have significant implications in the design and investigation of effective vaccine strategies and immunotherapeutic approaches for individuals who have been pre-immunized with BCG vaccine but still get infected with Mtb.

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Section: Discussionmentioning

confidence: 99%

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

et al. 2018

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“…While CD8 + T cells are critical for the control of viral and some bacterial infections, their role in immunity against mycobacteria is less clear. T‐cell adoptive transfer studies and studies in gene‐deficient mice support a role for CD8 + T cells in containment of M. tuberculosis infection, particularly during the chronic stage (reviewed in Reference ). In mice, BCG is a poor stimulator of CD8 + T‐cell responses compared with M. tuberculosis and this is the rationale for the development of vaccines targeting CD8 + T‐cell expansion .…”

Section: New Tb Vaccine Candidates and T‐cell Memorymentioning

confidence: 99%

The generation of T‐cell memory to protect against tuberculosis

Counoupas

Triccas

2019

Immunol Cell Biol

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Tuberculosis (TB) kills more individuals each year than any other single pathogen and a more effective vaccine is critical for the global control of the disease. Although there has been recent progress in the clinical testing of candidates, no new vaccine has been licensed for use and correlates of protective immunity in humans have not been defined. Prior Mycobacterium tuberculosis infection does not appear to confer long‐term protective immunity in humans; thus mimicking the natural immune response to infection may not be a suitable approach to develop improved TB vaccines. Data from animal testing are used to progress vaccines through the “vaccine pipeline”, but studies in animals have not been able to predict efficacy in humans. Furthermore, although the generation of conventional CD4+ T‐cell responses are considered necessary to control infection with M. tuberculosis, these do not necessarily correlate with protection induced by candidate vaccines and other immune components may play a role, including donor unrestricted T cells, tissue‐resident memory T cells and anti‐M. tuberculosis antibodies. This review will summarize the current understanding of the protective immune responses following M. tuberculosis infection or vaccination, with a particular focus on vaccines that have recently entered clinical trials.

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“…Likewise, some immunogenic peptide antigens have been proposed as immunotherapy candidates for inducing cytotoxic activity in TB drug‐resistant patients . Thus, it has now been accepted that CD8 + T cells play a critical role in the immune response against Mtb infection, as reviewed by Lin and Flynn …”

Section: Introductionmentioning

confidence: 99%

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

Chávez‐Galán

Illescas‐Eugenio

Álvarez-Sekely

et al. 2019

Microbiology and Immunology

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major cause of morbidity and mortality worldwide. In the host's immune response system, T cells play a critical role in mediating protection against Mtb infection, but the role of CD8+ T cells is still controversial. We evaluated the phenotypical characterization and cytotoxic ability of CD8+ T cells by flow cytometry‐based assay. Cytokine levels in serum were measured by multiplex cytokine assay. Our data show that cells from TB patients have an increased percentage of peripheral blood CD8+αβ+ T (p = 0.02) and CD56+CD8+ T (p = 0.02) and a decreased frequency of NKG2D+CD8+ T (p = 0.02) compared with healthy donors. Unlike CD8+ T cells from healthy donors, CD8+ T cells from TB patients exhibit greater cytotoxicity, mediated by HLA class I molecules, on autologous monocytes in the presence of mycobacterial antigens (p = 0.005). Finally, TB patients have a proinflammatory profile characterized by serum high level of TNF‐α (p = 0.02) and IL‐8 (p = 0.0001), but, interestingly, IL‐4 (p = 0.002) was also increased compared with healthy donors. Our data show evidence regarding the highly cytotoxic status of CD8+ T cells in Mtb infection. These cytotoxic cells restricted to HLA‐A, B, and C could be used to optimize strategies for designing new TB vaccines or for identifying markers of disease progression.

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CD8 T cells and Mycobacterium tuberculosis infection

Cited by 185 publications

References 81 publications

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

The generation of T‐cell memory to protect against tuberculosis

Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential

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CD8 T cells and Mycobacterium tuberculosis infection

Cited by 185 publications

References 81 publications

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

The generation of T‐cell memory to protect against tuberculosis

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential

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Tuberculosis patients display a high proportion of CD8⁺ T cells with a high cytotoxic potential