The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8<sup>+</sup>T Cells

Satchidanandam, Vijaya; Kumar, Naveen; Biswas, Sunetra; Jumani, Rajiv S.; Jain, Chandni; Rani, Rajni; Aggarwal, Bharti; Singh, Jaya; Kotnur, Mohan Rao; Sridharan, Anand

doi:10.1128/cvi.00554-15

Cited by 13 publications

(20 citation statements)

References 68 publications

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“…Using an in vitro model, it has been demonstrated that LAM has a direct effect on cells, affecting cellular differentiation and functionality . It has recently been suggested that the generation of TB vaccines carrying CD8 + T cells stimulates antigens that have the potential to prevent the progression of latent TB infection to TB diseases . Thus, our results provide new knowledge regarding the status of CD8 + cells in peripheral blood under Mtb infection.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

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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“…Definitions for LTBI patients were heterogeneous and highly variable across studies. Overall 14/34 (41%) studies included a control group of healthy participants who had negative test results for interferon gamma-release assays /tuberculin skin test and/or no known history of or exposure to aTB ( 19 , 22 , 24 , 28 , 29 , 32 , 34 , 35 , 37 , 38 , 43 , 47 , 48 , 50 ). A further 2/34 (6%) studies included exposed individuals into the control group as long as they stayed healthy (e.g., no symptoms and microbiologically negative or tuberculin skin test negative) ( 32 , 34 ).…”

Section: Resultsmentioning

confidence: 99%

“…Antigens of the Ag85 complex (Ag85A, Ag85B, Ag85C) have been extensively studied and were included in a number of studies selected in this review. In the newer studies those antigens were mostly included as “classical” and “reference” antigens ( 29 , 39 , 41 , 48 ), however three older studies, recruiting patients in South America reported more in-depth results ( 18 , 19 , 49 ). Schwander et al reported stimulation with Ag85A and Ag85B resulted in significantly higher IFN-γ producing T cells in both PBMCs and broncho-alveolar cells of household contacts in a short-term assay compared to healthy controls ( 49 ).…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review on Novel Mycobacterium tuberculosis Antigens and Their Discriminatory Potential for the Diagnosis of Latent and Active Tuberculosis

et al. 2018

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Background: Current immunodiagnostic tests for tuberculosis (TB) are based on the detection of an immune response toward mycobacterial antigens injected into the skin or following an in-vitro simulation in interferon gamma-release assays. Both tests have limited sensitivity and are unable to differentiate between tuberculosis infection (LTBI) and active tuberculosis disease (aTB). To overcome this, the use of novel Mycobacterium tuberculosis (M. tuberculosis) stage-specific antigens for the diagnosis of LTBI and aTB has gained interest in recent years. This review summarizes current evidence on novel antigens used for the immunodiagnosis of tuberculosis and discrimination of LTBI and aTB. In addition, results on measured biomarkers after stimulation with novel M. tuberculosis antigens were also reviewed.Methods: A systematic literature review was performed in Pubmed, EMBASE and web of science searching articles from 2000 up until December 2017. Only articles reporting studies in humans using novel antigens were included.Results: Of 1,533 articles screened 34 were included in the final analysis. A wide range of novel antigens expressed during different stages and types of LTBI and aTB have been assessed. M. tuberculosis antigens Rv0081, Rv1733c, Rv1737c, Rv2029c, Rv2031 and Rv2628, all encoded by the dormancy of survival regulon, were among the most widely studied antigens and showed the most promising results. These antigens have been shown to have best potential for differentiating LTBI from aTB. In addition, several studies have shown that the inclusion of cytokines other than IFN-γ can improve sensitivity.Conclusion: There is limited evidence that the inclusion of novel antigens as well as the measurement of other biomarkers than IFN-γ may improve sensitivity and may lead to a discrimination of LTBI from aTB.

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“…Diduga perbedaan HLA menyebabkan respons imun yang berbeda pada tiap individu. 30 Kadar IL-4 Pasca Stimulasi Antigen Fusi rESAT-6-CFP-10 pada kelompok TB aktif, TB laten dan orang sehat Kadar IL-4 pasca stimulasi pada kelompok TB laten lebih rendah dibandingkan TB aktif karena mekanisme sistem imun yang menghambat produksi IL-4 pasca stimulasi dengan antigen spesifik Th1. Produksi sitokin IL-4 dihambat oleh IFN-γ dan IL-2 pada kadar yang tinggi pada orang sehat maupun TB laten berperan aktif untuk menghambat produksi IL-4.…”

Section: Kadar Tnf-α Pasca Stimulasi Antigen Fusi Resat-6-cfp-10 Padaunclassified

Respons Sitokin TNF-Α Dan Il-4 Pasca Stimulasi Antigen Fusi Resat-6-CFP-10

Pratiwi¹,

Nugraha²,

Tambunan³

et al. 2018

bpk

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Protective immunity of tuberculosis (TB) infection is highly dependent on the balance of Th1 and Th2cytokines. TNF-α cytokines produced by Th1 cell retain a latent status, and IL-4 produced by Th2 aidsin the production of antibodies. The recent development of the vaccine candidates shows that rESAT-6-CFP-10 fusion antigen is specific to induce protective immune responses. The objective of the study wasto determine the immune response. This study used a quasi experimental design in the laboratory in vitrowith cultured PBMC of patients with new cases of pulmonary TB, latent TB and healthy individuals.Examination of TNF-α and IL-4 levels was done by ELISA. The highest TNF-α mean levels were 866,05in the latent TB group, compared to 814,56 in active TB and 414,58 in healthy individuals, but they werenot significantly different. The highest IL-4 mean levels were 1,39 in the active TB group, compared to0,88 in latent TB and 0,74 in healthy individuals, but they were not significantly different. High levels ofTNF-α and low levels of Il-4 in latent TB post-stimulation of rESAT-6-CFP-10 fusion antigen show thatthe candidate vaccine is capable of providing protective reponse against Mycobacterium tuberculosisinfection.Key words : TNF-α, IL-4, PBMC, ELISA, rESAT-6-CFP-10 AbstrakImunitas protektif terhadap infeksi tuberculosis sangat bergantung terhadap keseimbangan sitokinT-helper (Th)-1 dan Th2. Sitokin TNF-α yang disekresi oleh sel Th1 mampu mempertahankan status laten,dan IL-4 yang disekresi oleh Th2 membantu produksi antibodi. Pengembangan kandidat vaksin terbaruyaitu antigen fusi rESAT-6-CFP-10 bersifat spesifik terhadap respons imun protektif. Tujuan penelitianini untuk mengetahui respons imun seluler melalui kadar TNF-α dan IL-4 pasca stimulasi antigen fusirESAT-6-CFP-10. Penelitian ini menggunakan desain eksperimen semu di laboratorium secara in vitropada kultur PBMC. Pemeriksaan kadar sitokin TNF-α dan IL-4 dengan metode ELISA. Rerata kadarTNF-α pasca stimulasi paling tinggi ditemukan pada kelompok TB laten 866,05, dibandingkan TBaktif 814,56 dan orang sehat 414,58, tetapi tidak berbeda bermakna. Reratakadar IL-4 pasca stimulasipaling tinggi ditemukan pada kelompok TB aktif, dibandingkan TB laten dan orang sehat, tetapi tidakberbeda bermakna. Kadar TNF-α yang tinggi dan kadar IL-4 yang rendah pada TB laten pasca stimulasiantigen fusi rESAT-6-CFP-10 menunjukkan bahwa kandidat vaksin mampu memberikan repons protektifterhadap infeksi Mycobacterium tuberculosis secara invitro.Kata kunci : TNF-α, IL-4, PBMC, ELISA, rESAT-6-CFP-10.

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The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8⁺T Cells

Cited by 13 publications

References 68 publications

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

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

A Systematic Review on Novel Mycobacterium tuberculosis Antigens and Their Discriminatory Potential for the Diagnosis of Latent and Active Tuberculosis

Respons Sitokin TNF-Α Dan Il-4 Pasca Stimulasi Antigen Fusi Resat-6-CFP-10

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The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8+T Cells

Cited by 13 publications

References 68 publications

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

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

A Systematic Review on Novel Mycobacterium tuberculosis Antigens and Their Discriminatory Potential for the Diagnosis of Latent and Active Tuberculosis

Respons Sitokin TNF-Α Dan Il-4 Pasca Stimulasi Antigen Fusi Resat-6-CFP-10

Contact Info

Product

Resources

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The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8⁺T Cells

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

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