title: Immune responses to tuberculosis in developing countries: implications for new vaccines.
abstract: Tuberculosis is out of control in developing countries, where it is killing millions of people every year. In these areas, the present vaccine - Mycobacterium bovis bacillus Calmette-Guérin (BCG) - is failing. Progressive tuberculosis occurs because the potentially protective T helper 1 (T(H)1)-cell response is converted to an immunopathological response that fails to eliminate the bacteria. Here, we discuss the data indicating that the problem in developing countries is not a lack of adequate T(H)1-cell responses but, instead, an exaggerated tendency to switch to immunopathological responses. We propose that a successful vaccine needs to block this immunopathology, because it is not the quantity of T(H)1-cell activity that matters but, rather, its context.
authors.affiliation: Centre for Infectious Diseases and International Health, Windeyer Institute for Medical Sciences, University College London, London W1T 4JF, UK. g.rook@ucl.ac.uk
authors.forename: Graham A W
authors.initials: GA
authors.lastname: Rook
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001500:BCG Vaccine / Q000627:therapeutic use; D019049:Developed Countries; D003906:Developing Countries; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma