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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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