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* Armauer Hansen Research Institute, Addis Ababa, Ethiopia;
Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark;
Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, London, United Kingdom; and
The VACSEL Study Group also includes: University of Zambia School of Medicine, Lusaka, Zambia: Prof. Chifumbe Chintu, Gina Mulundu, Dr. Peter Mwaba. Medical Research Council, Gambia: Prof. K. P.W. J. McAdam, Patrick Owiafe, Dr. David Warndorff, Dr. Christian Lienhardt, Dr. R Brookes, Dr. Phillip Hill
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop disease and identifying what constitutes "protective immunity" is one of the holy grails of M. tuberculosis immunology. It is known that IFN-
is essential for protection, but it is also apparent that IFN- levels alone do not explain the immunity/susceptibility dichotomy. The controversy regarding correlates of immunity persists because identifying infected but healthy individuals (those who are immune) has been problematic. We have therefore used recognition of the M. tuberculosis virulence factor early secretory antigenic target 6 to identify healthy, but infected individuals from tuberculosis (TB)-endemic and nonendemic regions (Ethiopia and Denmark) and have compared signals for cytokines expressed directly ex vivo with the pattern found in TB patients. We find that TB patients are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected community controls. Interestingly, the healthy infected subjects exhibited a selective increase of message for the IL-4 antagonist, IL-4
2, compared with both TB patients or noninfected individuals. These data suggest that long-term control of M. tuberculosis infection is associated not just with elevated Th1 responses but also with inhibition of the Th2 response.
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