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Infection and Immunity, December 2002, p. 6707-6714, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6707-6714.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

T-Cell Responses to the Mycobacterium tuberculosis-Specific Antigen ESAT-6 in Brazilian Tuberculosis Patients

Fernando L. L. Cardoso,1,2 Paulo R. Z. Antas,1 Alexandre S. Milagres,3 Annemieke Geluk,4 Kees L. M. C. Franken,4 Eliane B. Oliveira,1 Henrique C. Teixeira,5 Susie A. Nogueira,2 Euzenir N. Sarno,1 Paul Klatser,6 Tom H. M. Ottenhoff,4 and Elizabeth P. Sampaio1*

Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ,1 Department of Infectious and Parasitic Diseases, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro,2 Department of Lung Diseases, Hospital Municipal Raphael de Paula e Souza, Rio de Janeiro,3 Laboratory of Immunology, Federal University of Juiz de Fora, Juiz de Fora, Brazil,5 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden,4 Department of Biomedical Research, Royal Tropical Institute, Amsterdam, The Netherlands6

Received 28 January 2002/ Returned for modification 3 April 2002/ Accepted 11 September 2002

The Mycobacterium tuberculosis-specific ESAT-6 antigen induces highly potent T-cell responses and production of gamma interferon (IFN-{gamma}), which play a critical role in protective cell-mediated immunity against tuberculosis (TB). In the present study, IFN-{gamma} secretion by peripheral blood mononuclear cells (PBMCs) in response to M. tuberculosis ESAT-6 in Brazilian TB patients was investigated in relation to clinical disease types, such as pleurisy and cavitary pulmonary TB. Leprosy patients, patients with pulmonary diseases other than TB, and healthy donors were assayed as control groups. Sixty percent of the TB patients indeed recognized M. tuberculosis ESAT-6, as did 50% of the leprosy patients and 60% of the non-TB controls. Nevertheless, the levels of IFN-{gamma} in response to the antigen ESAT, but not to antigen 85B (Ag85B) and purified protein derivative (PPD), were significantly lower in controls than in patients with treated TB or pleural or cavitary TB. Moreover, according to Mycobacterium bovis BCG vaccination status, only 59% of the vaccinated TB patients responded to ESAT in vitro, whereas 100% of them responded to PPD. Both CD4 and CD8 T cells were able to release IFN-{gamma} in response to ESAT. The present data demonstrate the specificity of ESAT-6 of M. tuberculosis and its ability to discriminate TB patients from controls, including leprosy patients. However, to obtain specificity, it is necessary to include quantitative IFN-{gamma} production in response to the antigen as well, and this might limit the use of ESAT-6-based immunodiagnosis of M. tuberculosis infection in an area of TB endemicity.

* Corresponding author. Mailing address: Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ-Av. Brasil, 4365 Manguinhos, Rio de Janeiro, Brazil 21045-900. Phone: 55 21 598-4287. Fax: (021) 270-9997. E-mail: esampaio{at}gene.dbbm.fiocruz.br.

Editor: S. H. E. Kaufmann

Infection and Immunity, December 2002, p. 6707-6714, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6707-6714.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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