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Infect Immun. Jul 1997; 65(7): 2587–2592.
PMCID: PMC175366

Predominant recognition of the ESAT-6 protein in the first phase of interferon with Mycobacterium bovis in cattle.

Abstract

Tuberculosis continues to be a worldwide health problem for both humans and animals. The development of improved vaccines and diagnostic tests requires detailed understanding of the immune responses generated and the antigens recognized during the disease. This study examined the T-cell response which develops in cattle experimentally infected with Mycobacterium bovis. The first significant T-cell response was found 3 weeks after the onset of infection and was characterized by a pronounced gamma interferon (IFN-gamma) response from peripheral blood mononuclear cells directed to antigens in culture filtrates. Short-term culture filtrate (ST-CF) was separated into molecular mass fractions and screened for recognition by T cells from experimentally infected and field cases of bovine tuberculosis. Cattle in the early stages of experimental infection were characterized by strong IFN-gamma responses directed predominantly toward the lowest-mass (<10-kDa) fraction of ST-CF, but cattle in later stages of experimental infection (16 weeks postinfection) exhibited a broader recognition of antigens of various molecular masses. Field cases of bovine tuberculosis, in comparison, preferentially recognized low-mass antigens, characteristic of animals in the early stages of infection. The major T-cell target for this dominant IFN-gamma response was found to be the secreted antigen ESAT-6. This antigen was recognized strongly by the majority of field cases of bovine tuberculosis tested. As ESAT-6 is unique to pathogenic mycobacterial species, our study suggests that ESAT-6 is an antigen with major potential for vaccination against and specific diagnosis of bovine tuberculosis.

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Selected References

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  • Alavi MR, Affronti LF. Induction of mycobacterial proteins during phagocytosis and heat shock: a time interval analysis. J Leukoc Biol. 1994 May;55(5):633–641. [PubMed]
  • Andersen AB, Andersen P, Ljungqvist L. Structure and function of a 40,000-molecular-weight protein antigen of Mycobacterium tuberculosis. Infect Immun. 1992 Jun;60(6):2317–2323. [PMC free article] [PubMed]
  • Andersen AB, Ljungqvist L, Hasløv K, Bentzon MW. MPB 64 possesses 'tuberculosis-complex'-specific B- and T-cell epitopes. Scand J Immunol. 1991 Sep;34(3):365–372. [PubMed]
  • Andersen P. Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins. Infect Immun. 1994 Jun;62(6):2536–2544. [PMC free article] [PubMed]
  • Andersen P, Heron I. Simultaneous electroelution of whole SDS-polyacrylamide gels for the direct cellular analysis of complex protein mixtures. J Immunol Methods. 1993 May 5;161(1):29–39. [PubMed]
  • Andersen P, Heron I. Specificity of a protective memory immune response against Mycobacterium tuberculosis. Infect Immun. 1993 Mar;61(3):844–851. [PMC free article] [PubMed]
  • Andersen P, Askgaard D, Ljungqvist L, Bentzon MW, Heron I. T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis. Infect Immun. 1991 Apr;59(4):1558–1563. [PMC free article] [PubMed]
  • Andersen P, Askgaard D, Ljungqvist L, Bennedsen J, Heron I. Proteins released from Mycobacterium tuberculosis during growth. Infect Immun. 1991 Jun;59(6):1905–1910. [PMC free article] [PubMed]
  • Andersen P, Andersen AB, Sørensen AL, Nagai S. Recall of long-lived immunity to Mycobacterium tuberculosis infection in mice. J Immunol. 1995 Apr 1;154(7):3359–3372. [PubMed]
  • Boesen H, Jensen BN, Wilcke T, Andersen P. Human T-cell responses to secreted antigen fractions of Mycobacterium tuberculosis. Infect Immun. 1995 Apr;63(4):1491–1497. [PMC free article] [PubMed]
  • Brandt L, Oettinger T, Holm A, Andersen AB, Andersen P. Key epitopes on the ESAT-6 antigen recognized in mice during the recall of protective immunity to Mycobacterium tuberculosis. J Immunol. 1996 Oct 15;157(8):3527–3533. [PubMed]
  • Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993 Dec 1;178(6):2243–2247. [PMC free article] [PubMed]
  • Daborn CJ, Grange JM. HIV/AIDS and its implications for the control of animal tuberculosis. Br Vet J. 1993 Sep-Oct;149(5):405–417. [PubMed]
  • Fifis T, Corner LA, Rothel JS, Wood PR. Cellular and humoral immune responses of cattle to purified Mycobacterium bovis antigens. Scand J Immunol. 1994 Mar;39(3):267–274. [PubMed]
  • Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993 Dec 1;178(6):2249–2254. [PMC free article] [PubMed]
  • Flynn JL, Goldstein MM, Triebold KJ, Koller B, Bloom BR. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013–12017. [PMC free article] [PubMed]
  • Harboe M, Oettinger T, Wiker HG, Rosenkrands I, Andersen P. Evidence for occurrence of the ESAT-6 protein in Mycobacterium tuberculosis and virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG. Infect Immun. 1996 Jan;64(1):16–22. [PMC free article] [PubMed]
  • Hasløv K, Andersen A, Nagai S, Gottschau A, Sørensen T, Andersen P. Guinea pig cellular immune responses to proteins secreted by Mycobacterium tuberculosis. Infect Immun. 1995 Mar;63(3):804–810. [PMC free article] [PubMed]
  • Horwitz MA, Lee BW, Dillon BJ, Harth G. Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1530–1534. [PMC free article] [PubMed]
  • Ladel CH, Blum C, Dreher A, Reifenberg K, Kaufmann SH. Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis. Eur J Immunol. 1995 Oct;25(10):2877–2881. [PubMed]
  • Ladel CH, Daugelat S, Kaufmann SH. Immune response to Mycobacterium bovis bacille Calmette Guérin infection in major histocompatibility complex class I- and II-deficient knock-out mice: contribution of CD4 and CD8 T cells to acquired resistance. Eur J Immunol. 1995 Feb;25(2):377–384. [PubMed]
  • Lee BY, Horwitz MA. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis. J Clin Invest. 1995 Jul;96(1):245–249. [PMC free article] [PubMed]
  • Lefford MJ. Transfer of adoptive immunity to tuberculosis in mice. Infect Immun. 1975 Jun;11(6):1174–1181. [PMC free article] [PubMed]
  • Lindblad EB, Elhay MJ, Silva R, Appelberg R, Andersen P. Adjuvant modulation of immune responses to tuberculosis subunit vaccines. Infect Immun. 1997 Feb;65(2):623–629. [PMC free article] [PubMed]
  • Mackaness GB, Blanden RV. Cellular immunity. Prog Allergy. 1967;11:89–140. [PubMed]
  • Neill SD, O'Brien JJ, Hanna J. A mathematical model for Mycobacterium bovis excretion from tuberculous cattle. Vet Microbiol. 1991 Jun;28(1):103–109. [PubMed]
  • Oettinger T, Holm A, Mtoni IM, Andersen AB, Hasløov K. Mapping of the delayed-type hypersensitivity-inducing epitope of secreted protein MPT64 from Mycobacterium tuberculosis. Infect Immun. 1995 Dec;63(12):4613–4618. [PMC free article] [PubMed]
  • Orme IM. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J Immunol. 1988 May 15;140(10):3589–3593. [PubMed]
  • Orme IM, Andersen P, Boom WH. T cell response to Mycobacterium tuberculosis. J Infect Dis. 1993 Jun;167(6):1481–1497. [PubMed]
  • Pollock JM, Douglas AJ, Mackie DP, Neill SD. Peptide mapping of bovine T-cell epitopes for the 38 kDa tuberculosis antigen. Scand J Immunol. 1995 Jan;41(1):85–93. [PubMed]
  • Pollock JM, Pollock DA, Campbell DG, Girvin RM, Crockard AD, Neill SD, Mackie DP. Dynamic changes in circulating and antigen-responsive T-cell subpopulations post-Mycobacterium bovis infection in cattle. Immunology. 1996 Feb;87(2):236–241. [PMC free article] [PubMed]
  • Roberts AD, Sonnenberg MG, Ordway DJ, Furney SK, Brennan PJ, Belisle JT, Orme IM. Characteristics of protective immunity engendered by vaccination of mice with purified culture filtrate protein antigens of Mycobacterium tuberculosis. Immunology. 1995 Jul;85(3):502–508. [PMC free article] [PubMed]
  • Sørensen AL, Nagai S, Houen G, Andersen P, Andersen AB. Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis. Infect Immun. 1995 May;63(5):1710–1717. [PMC free article] [PubMed]
  • Wood PR, Corner LA, Rothel JS, Baldock C, Jones SL, Cousins DB, McCormick BS, Francis BR, Creeper J, Tweddle NE. Field comparison of the interferon-gamma assay and the intradermal tuberculin test for the diagnosis of bovine tuberculosis. Aust Vet J. 1991 Sep;68(9):286–290. [PubMed]

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