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Infection and Immunity, December 1998, p. 5743-5750, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mycobacterial Dose Defines the Th1/Th2 Nature of the Immune Response Independently of Whether Immunization Is Administered by the Intravenous, Subcutaneous, or Intradermal Route

Carl A. Power, Guojian Wei, and Peter A. Bretscher*

Department of Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5 Canada

Received 27 April 1998/Returned for modification 28 May 1998/Accepted 1 September 1998

It is believed that cell-mediated immunity alone can contain Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. The induction of antibody, or of a mixed cell-mediated/humoral response, is associated with tuberculous disease. It is therefore important to determine the conditions of immunization with bacille Calmette Guérin (BCG), the attenuated strain of Mycobacterium bovis used to vaccinate humans against tuberculosis, that optimally induces an exclusive cell-mediated, Th1 response. Such a determination will then allow an assessment of whether the generation of such an exclusive Th1 response results in the generation of a Th1 imprint against mycobacteria. This Th1 imprint would ensure that the Th1 response is predominant following any challenge. We therefore tested the proposition that the dose of mycobacteria used for immunization generally determines the Th1/Th2 nature of the ensuing response. Our results demonstrate that relatively low doses lead to an almost exclusive cell-mediated, Th1 response, while higher doses induce a mixed Th1/Th2 response. Furthermore, the dependence on dose is independent of whether BCG is administered intravenously, subcutaneously, or intradermally. The implications of our findings to understanding how different classes of immunity are induced, to the epidemiology of tuberculosis, and to the design of effective vaccination strategies are discussed.

* Corresponding author. Mailing address: Department of Microbiology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada. Phone: (306) 665-4322. Fax: (306) 966-4311. E-mail: bretschr{at}duke.usask.ca.

Infection and Immunity, December 1998, p. 5743-5750, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.