The production of granzima B and interferon gamma by L ymphocytes T infected with Mycobacterium tuberculosis in vitro
Claudia Carranza, Esmeralda Juárez, Ma del Carmen Sarabia, Dante Escobedo, Eduardo Sada, Martha Torres
2010, Number 2
2010; 69 (2)
ABSTRACT
Background: The effectors cytotoxic molecules like granzima B (GrB), participate in the defense at the infection by Mycobacterium tuberculosis (M. tuberculosis), nevertheless, has not been studied their participation in the control of the infection with M. tuberculosis in the human. Methods: The production of GrB and IFNα in mononuclear cells of peripheral blood cells and bronchoalveolar cells from healthy donors PPD+ and PPD- was assessed by ELISPOT and cellular activation was analyzed by FACS. Results:M. tuberculosis, and PPD, induces the IFNα production by mononuclear cells and bronchoalveolar cells. The frequency of producing cells of GrB in mononuclear and bronchoalveolar cells was low when comparing itself with the producing cells of IFNα. Conclusions: The frequency of producing cells of IFN-α was higher in mononuclear and bronchoalveolar cells from healthy donors PPD+ in comparison with PPD-. In contrast the frequency of producing cells of GrB was low and comparable in both groups. These results suggest that the previous exposition to M. tuberculosis induces the activation of the acquired mechanisms as IFN-α without the participation of cytotoxic mechanisms. The determination of IFN-α by ELISPOT could be a useful biomarker to the study of immune protection in human tuberculosis.
Sepkowitz KA. How contagious is tuberculosis? Clin Infect Dis 1996;23:954-962.
Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol 2001;19:93-129.
Giacomini E, Iona E, Ferroni L, et ál. Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response. J Immunol 2001;166:7033-7041.
Torres M, Herrera T, Villareal H, Rich E, Sada E. Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect Immun 1998;66:176-180.
Caruso A, Serbina N, Klein E, Triebold K, Bloom B, Flynn J. Mice deficient in CD4 T cells have only transiently diminished levels of INF-g, yet succumb to tuberculosis. J Immunol 1999;162:5407-5416.
Flynn J, Chan J, Triebold K, Dalton D, Stewart TA, Bloom BR. An essential role for IFN - g in resistance to Mycobacterium tuberculosis. J Exp Med 1993;178: 2249-2251.
Russell JH, Ley TJ. Lymphocyte-mediated cytotoxicity. Annu Rev Immunol 2002;20:323-370.
Schwander S, Torres M, Carranza C, et ál. Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in healthy household contacts of patients with active tuberculosis and healthy controls from the community. J Immunol 2000;165:1479-1485.
Carranza C, Juárez E, Torres M, Ellner J, Sada E, Schwander SK. Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. Am J Respir Crit Care Med 2006;173:238-245.
Tan JS, Canaday DH, Boom WH, Balaji KN, Schwander SK, Rich EA. Human alveolar T lymphocyte responses to Mycobacterium tuberculosis antigens: role for CD4+ and CD8+ cytotoxic T cells and relative resistance of alveolar macrophages to lysis. J Immunol 1997;159:290-297.
Brookes RH, Pathan AA, McShane H, Hensmann M, Price DA, Hill AV. CD8+ T cell-mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages. Eur J Immunol 2003;33:3293-3302.
Serbina NV, Lazarevic V, Flynn JL. CD4(+) T cells are required for the development of cytotoxic CD8(+) T cells during Mycobacterium tuberculosis infection. J Immunol 2001;167:6991-7000.
Pathan AA, Wilkinson KA, Wilkinson RJ, et ál. High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis- infected subjects without disease. Eur J Immunol 2000;30:2713-2721.
Bachmann MF, Barner M, Viola A, Kopf M. Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection. Eur J Immunol 1999;29:291-299.
Wherry EJ, Teichgräber V, Becker TC, et ál. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003;4:225-234.
García-García ML, Small PM, García-Sancho C, et ál. Tuberculosis epidemiology and control in Veracruz, Mexico. Int J Epidemiol 1999;28:135-140.