- INTRODUCTION
- METHODS
- RESULTS
- Hematological parameters.
- Positive lymph node tuberculosis individuals are associated with altered cytokine responses in UNS LN supernatants.
- Positive lymph node tuberculosis individuals are associated with enhanced type 1 and type 17 cytokines on TB antigen (PPD, ESAT-6 PP, and CFP-10 PP) stimulation in LN supernatants.
- No significant differences in cytokine production on HIV GAG PP and P/I stimulation.
- Baseline and TB antigen stimulated type 1, type 17, regulatory, and IL-1 family or pro-inflammatory cytokines clearly distinguish LNTB+ from LNTB− individuals.
- DISCUSSION
- Supplementary Files
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Sharma SK, Mohan A, 2004. Extrapulmonary tuberculosis. Ind J Med Res 120: 316–353.
-
2.
Korea Centers for Disease Control and Prevention, 2014. Annual Report on the Notified Tuberculosis in Korea. Cheongwon, Korea: Korea Centers for Disease Control and Prevention, 2013.
-
3.
Gothi D, Jaswal A, Spalgais S, 2016. Lymph node tuberculosis. EC Pulmonol Respir Med 2.5: 194–211.
-
4.
Handa U, Mundi I, Mohan S, 2012. Nodal tuberculosis revisited: a review. J Infect Dev Ctries 6: 6–12.
-
5.
Knox J, Lane G, Wong JSJ, Trevan PG, Karunajeewa H, 2012. Diagnosis of tuberculous lymphadenitis using fine needle aspiration biopsy. Intern Med J 42: 1029–1036.
-
6.
Cooper AM, 2009. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27: 393–422.
-
7.
Arenas-Ramirez N, Woytschak J, Boyman O, 2015. Interleukin-2: biology, design and application. Trends Immunol 36: 763–777.
-
8.
Kolls JK, Khader SA, 2010. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev 21: 443–448.
-
9.
Dudakov JA, Hanash AM, van den Brink MR, 2015. Interleukin-22: immunobiology and pathology. Annu Rev Immunol 33: 747–785.
-
10.
O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP, 2013. The immune response in tuberculosis. Annu Rev Immunol 31: 475–527.
-
11.
Mayer-Barber KD, Sher A, 2015. Cytokine and lipid mediator networks in tuberculosis. Immunol Rev 264: 264–275.
-
12.
Rothchild AC, Jayaraman P, Nunes-Alves C, Behar SM, 2014. iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS Pathog 10: e1003805.
-
13.
Griffin JD, Cannistra SA, Sullivan R, Demetri GD, Ernst TJ, Kanakura Y, 1990. The biology of GM-CSF: regulation of production and interaction with its receptor. Int J Cell Cloning 8 (Suppl 1): 35–44 ; discussion 44–45.
-
14.
Ellner JJ, 2010. Immunoregulation in TB: observations and implications. Clin Transl Sci 3: 23–28.
-
15.
Bhatt K, Verma S, Ellner JJ, Salgame P, 2015. Quest for correlates of protection against tuberculosis. Clin Vaccine Immunol 22: 258–266.
-
16.
Kumar NP, Gopinath V, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2013. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis. PLoS One 8: e59572.
-
17.
Kumar NP, Sridhar R, Banurekha VV, Nair D, Jawahar MS, Nutman TB, Babu S, 2013. Expansion of pathogen-specific mono- and multifunctional Th1 and Th17 cells in multi- focal tuberculous lymphadenitis. PLoS One 8: e57123.
-
18.
Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2014. Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis. Tuberculosis (Edinb) 94: 482–493.
-
19.
Kathamuthu GR, Moideen K, Bhaskaran D, Sekar G, Sridhar R, Vidyajayanthi B, Gajendraraj G, Babu S, 2017. Reduced systemic and mycobacterial antigen-stimulated concentrations of IL-1β and IL-18 in tuberculous lymphadenitis. Cytokine 90: 66–72.
-
20.
Kathamuthu GR et al. 2017. Tuberculous lymphadenitis is associated with enhanced baseline and antigen-specific induction of type 1 and type 17 cytokines and reduced interleukin-1β (IL-1β) and IL-18 at the site of infection. Clin Vaccine Immunol 24: e00045-17.
-
21.
Cooper AM, Mayer-Barber KD, Sher A, 2011. A role of innate cytokines in mycobacterial infection. Mucosal Immunol 4: 252–260.
-
22.
Sahiratmadja E et al. 2007. Plasma granulysin levels and cellular interferon-gamma production correlate with curative host responses in tuberculosis, while plasma interferon-gamma levels correlate with tuberculosis disease activity in adults. Tuberculosis (Edinb) 87: 312–321.
-
23.
Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM, 1993. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178: 2243–2247.
-
24.
Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR, 1993. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178: 2249–2254.
-
25.
Nandi B, Behar SM, 2011. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J Exp Med 208: 2251–2262.
-
26.
Al-Attiyah R, El-Shazly A, Mustafa AS, 2012. Comparative analysis of spontaneous and mycobacterial antigen-induced secretion of Th1, Th2 and pro-inflammatory cytokines by peripheral blood mononuclear cells of tuberculosis patients. Scand J Immunol 75: 623–632.
-
27.
Kumar Nathella P, Babu S, 2017. Influence of diabetes mellitus on immunity to human tuberculosis. Immunology 152: 13–24.
-
28.
Millington KA, Gooding S, Hinks TS, Reynolds DJ, Lalvani A, 2010. Mycobacterium tuberculosis-specific cellular immune profiles suggest bacillary persistence decades after spontaneous cure in untreated tuberculosis. J Infect Dis 202: 1685–1689.
-
29.
Khader SA et al. 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8: 369–377.
-
30.
Jurado JO et al. 2012. IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease. J Leukoc Biol 91: 991–1002.
-
31.
Yang XO et al. 2008. Regulation of inflammatory responses by IL-17F. J Exp Med 205: 1063–1075.
-
32.
Scriba TJ et al. 2008. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180: 1962–1970.
-
33.
Mayer-Barber KD et al. 2014. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature 511: 99–103.
-
34.
Yamada H, Mizumo S, Horai R, Iwakura Y, Sugawara I, 2000. Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice. Lab Invest 80: 759–767.
-
35.
Ben-Sasson SZ et al. 2013. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med 210: 491–502.
-
36.
Ushach I, Zlotnik A, 2016. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 100: 481–489.
-
37.
Shi Y et al. 2006. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 16: 126–133.
-
38.
Rothchild AC et al. 2017. Role of granulocyte-macrophage colony-stimulating factor production by T cells during Mycobacterium tuberculosis infection. MBio 8: e01514-17.
-
39.
Kahnert A, Seiler P, Stein M, Bandermann S, Hahnke K, Mollenkopf H, Kaufmann SH, 2006. Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis. Eur J Immunol 36: 631–647.
-
40.
Harris J, De Haro SA, Master SS, Keane J, Roberts EA, Delgado M, Deretic V, 2007. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27: 505–517.
-
41.
Redford PS, Murray PJ, O’Garra A, 2011. The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol 4: 261–270.
-
42.
Hirsch CS, Ellner JJ, Blinkhorn R, Toossi Z, 1997. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta. Proc Natl Acad Sci USA 94: 3926–3393.
-
43.
Jafari C, Ernst M, Kalsdorf B, Greinert U, Diel R, Kirsten D, Marienfeld K, Lalvani A, Lange C, 2006. Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot. Am J Respir Crit Care Med 174: 1048–1054.
-
44.
Wilkinson KA, Wilkinson RJ, Pathan A, Ewer K, Prakash M, Klenerman P, Maskell N, Davies R, Pasvol G, Lalvani A, 2005. Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis. Clin Infect Dis 40: 184–187.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1515 | 1380 | 23 |
| Full Text Views | 578 | 6 | 0 |
| PDF Downloads | 201 | 10 | 0 |
Enhanced Mycobacterial Antigen–Induced Pro-Inflammatory Cytokine Production in Lymph Node Tuberculosis
Gokul Raj Kathamuthu
Gokul Raj Kathamuthu
National Institutes of Health, National Institute for Research in Tuberculosis (NIRT), International Center for Excellence in Research, Chennai, India;
National Institute for Research in Tuberculosis (NIRT), Chennai, India;
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National Institute for Research in Tuberculosis (NIRT), Chennai, India;
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Kadar Moideen
Kadar Moideen
National Institutes of Health, National Institute for Research in Tuberculosis (NIRT), International Center for Excellence in Research, Chennai, India;
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Rathinam Sridhar
Rathinam Sridhar
Government Stanley Medical Hospital, Chennai, India;
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Dhanaraj Baskaran
Dhanaraj Baskaran
National Institute for Research in Tuberculosis (NIRT), Chennai, India;
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Subash Babu
Subash Babu
National Institutes of Health, National Institute for Research in Tuberculosis (NIRT), International Center for Excellence in Research, Chennai, India;
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Lymph node tuberculosis (LNTB) is characterized by the enhanced baseline and antigen-specific production of type 1/17 cytokines and reduced baseline and antigen-specific production of interleukin (IL)-1β and IL-18 at the site of infection when compared with peripheral blood. However, the cytokine profile in the lymph nodes (LNs) of Mycobacterium tuberculosis culture–positive LNTB (LNTB+) and negative LNTB (LNTB−) has not been examined. To address this, we have examined the baseline and mycobacterial antigen–stimulated cytokine levels of type 1 (interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], IL-2), type 2 (IL-4, IL-5, and IL-13), type 17 (IL-17A, IL-17F, and IL-22), pro-inflammatory (IL-1α, IL-1β, IL-18, and granulocyte macrophage colony-stimulating factor [GM-CSF]), and regulatory cytokines (IL-10, transforming growth factor beta [TGF-β]) cytokines in the LN culture supernatants of LNTB+ and LNTB− individuals. We have observed significantly enhanced baseline levels of IL-13 and IL-10 and significantly reduced baseline levels of IL-4 and GM-CSF in LNTB+ individuals compared with LNTB− individuals. By contrast, we have observed significantly enhanced levels of type 1 (IFNγ, TNFα, and IL-2), type 17 (IL-17F and IL-22), and pro-inflammatory (IL-1α and GM-CSF) cytokines and significantly reduced levels of TGFβ in response to purified protein derivative, early secreted antigen-6, and culture filtrate protein-10 antigens in LNTB+ compared with LNTB− individuals. On phorbol 12-myristate 13-acetate/ionomycin stimulation, no significant difference was observed for any of the cytokines examined. Thus, our study revealed several interesting differences in the cytokine profiles of mycobacterial antigen–stimulated LN cultures in LNTB+ and LNTB− individuals. Therefore, we suggest the presence of mycobacteria plays a significant role in driving the cytokine response at the site of infection in LNTB.
- Supplemental Materials (PDF 1094 KB)
Author Notes
Financial support: This work was funded by the Division of Intramural Research, NIAID, NIH. I (G. R. K.) thank the Indian Council of Medical Research (ICMR) for providing the ICMR Postdoctoral Fellowship (PDF).
Authors’ addresses: Gokul Raj Kathamuthu, Kadar Moideen, and Subash Babu, National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research (NIH-NIRT-ICER), Chennai, India, E-mails: gokul.r@nirt.res.in, kadar.m@nirt.res.in, and sbabu@niaid.nih.gov. Rathinam Sridhar, Government Stanley Medical Hospital, Government Hospital of Thoracic Medicine, Chennai, India, E-mail: srihema.1964@gmail.com. Dhanaraj Baskaran, National Institute for Research in Tuberculosis, Chennai, India, E-mail: baskar.d@nirt.res.in.
- INTRODUCTION
- METHODS
- RESULTS
- Hematological parameters.
- Positive lymph node tuberculosis individuals are associated with altered cytokine responses in UNS LN supernatants.
- Positive lymph node tuberculosis individuals are associated with enhanced type 1 and type 17 cytokines on TB antigen (PPD, ESAT-6 PP, and CFP-10 PP) stimulation in LN supernatants.
- No significant differences in cytokine production on HIV GAG PP and P/I stimulation.
- Baseline and TB antigen stimulated type 1, type 17, regulatory, and IL-1 family or pro-inflammatory cytokines clearly distinguish LNTB+ from LNTB− individuals.
- DISCUSSION
- Supplementary Files
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Sharma SK, Mohan A, 2004. Extrapulmonary tuberculosis. Ind J Med Res 120: 316–353.
-
2.
Korea Centers for Disease Control and Prevention, 2014. Annual Report on the Notified Tuberculosis in Korea. Cheongwon, Korea: Korea Centers for Disease Control and Prevention, 2013.
-
3.
Gothi D, Jaswal A, Spalgais S, 2016. Lymph node tuberculosis. EC Pulmonol Respir Med 2.5: 194–211.
-
4.
Handa U, Mundi I, Mohan S, 2012. Nodal tuberculosis revisited: a review. J Infect Dev Ctries 6: 6–12.
-
5.
Knox J, Lane G, Wong JSJ, Trevan PG, Karunajeewa H, 2012. Diagnosis of tuberculous lymphadenitis using fine needle aspiration biopsy. Intern Med J 42: 1029–1036.
-
6.
Cooper AM, 2009. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27: 393–422.
-
7.
Arenas-Ramirez N, Woytschak J, Boyman O, 2015. Interleukin-2: biology, design and application. Trends Immunol 36: 763–777.
-
8.
Kolls JK, Khader SA, 2010. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev 21: 443–448.
-
9.
Dudakov JA, Hanash AM, van den Brink MR, 2015. Interleukin-22: immunobiology and pathology. Annu Rev Immunol 33: 747–785.
-
10.
O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP, 2013. The immune response in tuberculosis. Annu Rev Immunol 31: 475–527.
-
11.
Mayer-Barber KD, Sher A, 2015. Cytokine and lipid mediator networks in tuberculosis. Immunol Rev 264: 264–275.
-
12.
Rothchild AC, Jayaraman P, Nunes-Alves C, Behar SM, 2014. iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS Pathog 10: e1003805.
-
13.
Griffin JD, Cannistra SA, Sullivan R, Demetri GD, Ernst TJ, Kanakura Y, 1990. The biology of GM-CSF: regulation of production and interaction with its receptor. Int J Cell Cloning 8 (Suppl 1): 35–44 ; discussion 44–45.
-
14.
Ellner JJ, 2010. Immunoregulation in TB: observations and implications. Clin Transl Sci 3: 23–28.
-
15.
Bhatt K, Verma S, Ellner JJ, Salgame P, 2015. Quest for correlates of protection against tuberculosis. Clin Vaccine Immunol 22: 258–266.
-
16.
Kumar NP, Gopinath V, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2013. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis. PLoS One 8: e59572.
-
17.
Kumar NP, Sridhar R, Banurekha VV, Nair D, Jawahar MS, Nutman TB, Babu S, 2013. Expansion of pathogen-specific mono- and multifunctional Th1 and Th17 cells in multi- focal tuberculous lymphadenitis. PLoS One 8: e57123.
-
18.
Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2014. Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis. Tuberculosis (Edinb) 94: 482–493.
-
19.
Kathamuthu GR, Moideen K, Bhaskaran D, Sekar G, Sridhar R, Vidyajayanthi B, Gajendraraj G, Babu S, 2017. Reduced systemic and mycobacterial antigen-stimulated concentrations of IL-1β and IL-18 in tuberculous lymphadenitis. Cytokine 90: 66–72.
-
20.
Kathamuthu GR et al. 2017. Tuberculous lymphadenitis is associated with enhanced baseline and antigen-specific induction of type 1 and type 17 cytokines and reduced interleukin-1β (IL-1β) and IL-18 at the site of infection. Clin Vaccine Immunol 24: e00045-17.
-
21.
Cooper AM, Mayer-Barber KD, Sher A, 2011. A role of innate cytokines in mycobacterial infection. Mucosal Immunol 4: 252–260.
-
22.
Sahiratmadja E et al. 2007. Plasma granulysin levels and cellular interferon-gamma production correlate with curative host responses in tuberculosis, while plasma interferon-gamma levels correlate with tuberculosis disease activity in adults. Tuberculosis (Edinb) 87: 312–321.
-
23.
Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM, 1993. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178: 2243–2247.
-
24.
Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR, 1993. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178: 2249–2254.
-
25.
Nandi B, Behar SM, 2011. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J Exp Med 208: 2251–2262.
-
26.
Al-Attiyah R, El-Shazly A, Mustafa AS, 2012. Comparative analysis of spontaneous and mycobacterial antigen-induced secretion of Th1, Th2 and pro-inflammatory cytokines by peripheral blood mononuclear cells of tuberculosis patients. Scand J Immunol 75: 623–632.
-
27.
Kumar Nathella P, Babu S, 2017. Influence of diabetes mellitus on immunity to human tuberculosis. Immunology 152: 13–24.
-
28.
Millington KA, Gooding S, Hinks TS, Reynolds DJ, Lalvani A, 2010. Mycobacterium tuberculosis-specific cellular immune profiles suggest bacillary persistence decades after spontaneous cure in untreated tuberculosis. J Infect Dis 202: 1685–1689.
-
29.
Khader SA et al. 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8: 369–377.
-
30.
Jurado JO et al. 2012. IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease. J Leukoc Biol 91: 991–1002.
-
31.
Yang XO et al. 2008. Regulation of inflammatory responses by IL-17F. J Exp Med 205: 1063–1075.
-
32.
Scriba TJ et al. 2008. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180: 1962–1970.
-
33.
Mayer-Barber KD et al. 2014. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature 511: 99–103.
-
34.
Yamada H, Mizumo S, Horai R, Iwakura Y, Sugawara I, 2000. Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice. Lab Invest 80: 759–767.
-
35.
Ben-Sasson SZ et al. 2013. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med 210: 491–502.
-
36.
Ushach I, Zlotnik A, 2016. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 100: 481–489.
-
37.
Shi Y et al. 2006. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 16: 126–133.
-
38.
Rothchild AC et al. 2017. Role of granulocyte-macrophage colony-stimulating factor production by T cells during Mycobacterium tuberculosis infection. MBio 8: e01514-17.
-
39.
Kahnert A, Seiler P, Stein M, Bandermann S, Hahnke K, Mollenkopf H, Kaufmann SH, 2006. Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis. Eur J Immunol 36: 631–647.
-
40.
Harris J, De Haro SA, Master SS, Keane J, Roberts EA, Delgado M, Deretic V, 2007. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27: 505–517.
-
41.
Redford PS, Murray PJ, O’Garra A, 2011. The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol 4: 261–270.
-
42.
Hirsch CS, Ellner JJ, Blinkhorn R, Toossi Z, 1997. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta. Proc Natl Acad Sci USA 94: 3926–3393.
-
43.
Jafari C, Ernst M, Kalsdorf B, Greinert U, Diel R, Kirsten D, Marienfeld K, Lalvani A, Lange C, 2006. Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot. Am J Respir Crit Care Med 174: 1048–1054.
-
44.
Wilkinson KA, Wilkinson RJ, Pathan A, Ewer K, Prakash M, Klenerman P, Maskell N, Davies R, Pasvol G, Lalvani A, 2005. Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis. Clin Infect Dis 40: 184–187.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1515 | 1380 | 23 |
| Full Text Views | 578 | 6 | 0 |
| PDF Downloads | 201 | 10 | 0 |