[Frontiers in Bioscience 3, c27-33, May 1, 1998]
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CAVEAT LECTOR




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LURIEíS TUBERCLE-COUNT METHOD TO TEST TB VACCINE EFFICACY IN RABBITS

Arthur M. Dannenberg, Jr.

Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, School of Hygiene and Public Health; and the Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205

Received 3/9/98 Accepted 3/14/98

8. DOSE EFFECTS

Tuberculosis is a local disease (23-25), controlled by the lymphocytes and macrophages participating at sites containing the bacillus. Primary pulmonary lesions are usually separated from each other by numerous alveolar spaces. Therefore, we have always thought that their development was independent of each other. Recently, however, evidence is accumulating that each lesion has systemic effects that influence the development of other primary lesions that are developing simultaneously. Specifically, when numerous primary lesions are developing in the lung, the hostís ability to prevent the development of microscopic tubercles into grossly visible size is impaired (26); and/or when very few primary lesions are developing in the lung, the hostís ability to prevent the development of microscopic tubercles is enhanced (26).

These effects are apparently related to the prevalence of Th1 or Th2 immune-specific lymphocytes: Low infecting doses of intracellular microorganisms favor the beneficial Th1 immune response, and high-infecting doses favor the host-detrimental Th2 immune response (27). This systemic effect in acquired resistance to pulmonary tuberculosis is more fully discussed in reference (26). [An update on Th1 and Th2 cells is presented in references 28 and 29.]

A careful immunohistochemical study will be required to investigate whether the microscopic tubercles that do not reach grossly visible size are those that locally contain more Th1 cells (which produce both tissue-damaging DTH and macrophage-activating CMI); and/or whether the tubercles that do reach visible size are those that locally contain more Th2 cells (which can suppress the Th1 response).