Mycobacterial dose defines the Th1/Th2 nature of the immune response independently of whether immunization is administered by the intravenous, subcutaneous, or intradermal route

It is believed that cell-mediated immunity alone can contain Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. The induction of a ntibody, or of a mixed cell-mediated/humoral response, is associated,vith t uberculous disease. It is therefore important to determine the conditions o f immunization with bacille Calmette Guerin (ECG), the attenuated strain of Mycobacterium bovis used to vaccinate humans against tuberculosis, that op timally induces an exclusive cell-mediated, Th1 response. Such a determinat ion will then allow an assessment of whether the generation of such an excl usive Th1 response results in the generation of a Th1 imprint against mycob acteria. 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 nat ure of the ensuing response. Our results demonstrate that relatively low do ses lead to an almost exclusive cell-mediated, Th1 response, while higher d oses induce a mixed Th1/Th2 response. Furthermore, the dependence on dose i s independent of whether BCG is administered intravenously, subcutaneously, or intradermally. The implications of our findings to understanding how di fferent classes of immunity are induced, to the epidemiology of tuberculosi s, and to the design of effective vaccination strategies are discussed.