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On Cell Signalling Mechanism of Mycobaterium Leprae Soluble Antigen (MLSA) in Jurkat T Cells

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Abstract

We investigated the role of Mycobaterium leprae soluble antigen (MLSA) in the modulation of calcium signalling, phosphorylation of mitogen-activated protein (MAP) kinases and IL-2 mRNA expression in human Jurkat T cells. We observed that MLSA induced an increase in free intracellular calcium concentrations, [Ca2+] i , via opening CRAC (Ca2+-release activated- Ca2+) channels. Furthermore, MLSA failed to potentiate both thapsigargin- and anti-CD3 antibodies-induced capacitative calcium influx in Jurkat T cells. We observed that MLSA failed to affect the degree of phosphorylation of two MAP kinases, i.e., ERK1/ERK2, stimulated by anti-CD3 antibodies alone or phorbol 12-myristate 13-acetate (PMA) alone. In order to mimic co-stimulation of T cells, we stimulated them by both PMA and anti-CD3 antibodies. MLSA significantly curtailed the phosphorylation of ERK1/ERK2, stimulated by both PMA and anti-CD3 antibodies in Jurkat T cells. Also MLSA was found to reduce the transcription of IL-2 gene in PMA plus anti-CD3 antibodies-activated Jurkat T cells. Our finding demonstrates that Ca2+ influx via CRAC channels, inhibition of ERK1/ERK2 phosphorylation and IL-2 gene transcription may be implicated in immunosuppressive effects of MLSA antigen.

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Abbreviations

CRAC:

Ca2+-release activated-Ca2+

ERK:

extracellularly-regulated kinase

MAP:

mitogen-activated protein

MLSA:

M. leprae soluble antigen

PMA:

phorbol 12-myristate 13-acetate (PMA)

References

  1. Smith W: We need to know what is happening to the incidence of leprosy. Lepr Rev 68: 195–200, 1997

    PubMed  CAS  Google Scholar 

  2. World Health Organisation. Leprosy — Global situation. In: Weekly Epidemiol Rec 77: 1–8, 2002

    Google Scholar 

  3. Nath I, Singh R: The suppressive effect of M leprae on the in vitro proliferation responses of lymphocytes from patients with leprosy. Clin Exp Immunol 42: 203–210, 1980

    PubMed  CAS  Google Scholar 

  4. Kaplan G, Cohn ZA: Cellular immunity in lepromatous and tuberculoid leprosy. Immunol Lett 11: 205–209, 1985

    Article  PubMed  CAS  Google Scholar 

  5. Koster FT, Scollard DM, Umland ET, Fishbein DB, Hanly WC, Brennan PJ, Nelson KE: Cellular and humoral immune response to a phenolic glycolipid antigen (Phen GL-1) in patients with leprosy. Clin Microbiol 25: 551–556, 1987

    CAS  Google Scholar 

  6. Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR: Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254: 279–282, 1991

    PubMed  CAS  Google Scholar 

  7. Agrewala JN, Kumar B, Vohra H: Potential role of B7-1 and CD28 molecules in immunosuppression in leprosy. Clin Exp Immunol 111: 56–63, 1998

    Article  PubMed  CAS  Google Scholar 

  8. Nath I, Vemuri N, Reddi AL, Jain S, Brooks P, Colston MJ, Misra RS, Ramesh V: The effect of antigen presenting cells on the cytokine profiles of stable and relational Lepromatous leprosy patients. Immunol Lett 75: 69–76, 2000

    Article  PubMed  CAS  Google Scholar 

  9. Grinstein S. Dixon SJ: Ion transport membrane potential, and cytoplasmic pH in lymphocytes: changes during activation. Physiol Rev USA 69: 417–481, 1989

    CAS  Google Scholar 

  10. Germain RN: MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 76: 287–299, 1994

    Article  PubMed  CAS  Google Scholar 

  11. Cantrell D: T cell antigen receptor signal transduction pathways. Annu Rev Immunol 14: 259–274, 1996

    Article  PubMed  CAS  Google Scholar 

  12. Lewis RS, Cahalan MD: Potassium and calcium channels in lymphocytes. Annu Rev Immunol 13: 623–653, 1995

    Article  PubMed  CAS  Google Scholar 

  13. Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA: Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA. J Exp Med 173: 721–730. 1991

    Article  PubMed  CAS  Google Scholar 

  14. Ward GW: CD 28: A signalling perspective. J Biochem 318: 361–377, 1996

    CAS  Google Scholar 

  15. Sharma N, Sharma VK, Gupta A, Kaur I, Ganguly NK: Immunological defect in leprosy patients: Altered T-lymphocyte signals. FEMS Immunol Med Microbiol 23: 355–362, 1999

    Article  PubMed  CAS  Google Scholar 

  16. Sharma N, Sharma VK, Gupta A, Kaur I, Kaur S, Ganguly NK: Alteration in early biochemical events following T cell activation in leprosy patients. Clin Immunol Immunopathol 88: 142–149, 1998

    Article  PubMed  CAS  Google Scholar 

  17. Zea AH, Ochoa MT, Ghosh P, Longo DL, Alvord WG, Valderrama L, Falabella R, Harvey LK, Saravia N, Moreno LH, Ochoa AC: Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy. Infect Immun. 66: 499–504, 1998

    PubMed  CAS  Google Scholar 

  18. Grynkiewicz GM, Ponie M, Tsein RY: A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440–3450, 1985

    PubMed  CAS  Google Scholar 

  19. Nel, AE, Hanekom C, Rheeder A, Williams K, Pollack S, Katz R, Landreth GE: Stimulation of MAP-2 kinase activity in T-lymphocytes by anti-CD3 or antiTCR monoclonal antibody is partially dependent on protein kinase C. J. Immunol. 144: 2683–2689, 1990

    PubMed  CAS  Google Scholar 

  20. Tessier C, Hichami A, Khan NA: Implication of three isoforms of PLA(2) in human T-cell proliferation. FEBS Lett. 520: 111–116, 2002

    Article  PubMed  CAS  Google Scholar 

  21. Joshi B, Girdhar BK, Mohanty KK Beuria MK, Girdhar A, Sengupta U: Immunological profile of treated Lepromatous Leprosy patients. Int J Lep and Other Mycobac Dis 69: 195–203, 2001

    CAS  Google Scholar 

  22. Satish M, Bhutani LK, Sharma AK, Nath I: Monocyte-derived soluble suppressor factor(s) in patients with lepromatous leprosy. Infect Immun 42: 890–899, 1983

    PubMed  Google Scholar 

  23. Kang SM, Beverly B, Tran AC, Brorson K, Schwartz RH, Lenardo MJ, Lenardo MJ: Translocation by AP-1 is a molecular target of T cell clonal anergy. Science 257: 1134–1138, 1992

    PubMed  CAS  Google Scholar 

  24. Nghiem P, Gardener P, Schuman H: Interleukin-2 transcriptional block by multifunctional Ca2+/calmodulin kinase. Nature 371: 347–350, 1994

    Article  PubMed  CAS  Google Scholar 

  25. Bonin A, Khan NA: Regulation of calcium signalling by docosahexaenoic acid in human T-cells: Implication of CRAC channels. J. Lipid Res. 41: 277–284, 2000

    PubMed  CAS  Google Scholar 

  26. Denys A, Aires A, Hichami A, Khan NA: Thapsigargin phosphorylates MAP kinases by opening CRAC channels and PLD activation: Inhibitory action of docosahexaenoic acid. FEBS Lett. 564: 177–182, 2004

    Article  PubMed  CAS  Google Scholar 

  27. Zweifach A, Lewis RS: Mitogen regulated Ca2+ current of T-lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc. Natl. Acad. Sci. USA. 90: 6295–6299, 1993

    Article  PubMed  CAS  Google Scholar 

  28. Frantz B, Nordby EC, Bren G, Steffan N, Paya CV, Kincaid RL, Tocci MJ, O'Keefe SJ, O'Neill EA: Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B. EMBO J. 13: 861–870, 1994

    PubMed  CAS  Google Scholar 

  29. Fafutis-Morris M, Guillen-Vargas CM, Navarro-Fierros S, Alfaro-Bustamante F, Zaitzeva-Petrovna G, Daneri-Navarro A, Santoscoy-Tovar L, Armendariz-Borunda J: Addition of anti-CD28 antibodies restores PBMC proliferation and IFN gamma production in lepromatous leprosy patients. J Interferon Cytokine Res. 19: 1237–1243, 1999

    Article  PubMed  CAS  Google Scholar 

  30. Denys A, Hichami A, Khan NA: n-3 PUFAs modulate T-cell activation via protein kinase C-alpha and -epsilon and the NF-kappaB signaling pathway. J Lipid Res. 46: 752–758, 2005

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Central JALMA Institute for Leprosy and other Mycobacterial Diseases (ICMR), Taj Ganj, Agra, U.P, 282001, India

    Beenu Joshi, Pradeep Kumar Dagur & Utpal Sengupta

  2. UPRES Lipids and Nutrition, Université de Bourgogne, Faculté des Sciences de la vie, 6 Boulevard Gabriel, Dijon, 21000, France

    Sihem Khedouci, Aziz Hichami & Naim Akhtar Khan

Authors
  1. Beenu Joshi
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  2. Sihem Khedouci
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  3. Pradeep Kumar Dagur
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  4. Aziz Hichami
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  5. Utpal Sengupta
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  6. Naim Akhtar Khan
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Correspondence to Naim Akhtar Khan.

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Joshi, B., Khedouci, S., Dagur, P.K. et al. On Cell Signalling Mechanism of Mycobaterium Leprae Soluble Antigen (MLSA) in Jurkat T Cells. Mol Cell Biochem 287, 157–164 (2006). https://doi.org/10.1007/s11010-006-9132-8

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  • DOI: https://doi.org/10.1007/s11010-006-9132-8

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