THE HOST RESPONSE TO CALMETTE-GU]~RIN BACILLUS INFECTION IN MICE* BY R. V. BLANDEN,~ M. J. LEFFORD,§ A~m

BCG (Calmette-Gu6rin bacillus) is presumed to protect against tuberculosis by virtue of the specific immune response it provokes in the vaccinated subject, but the measurement of this response is beset with technicM problems. First, the tubercle bacillus, against which specific resistance must ultimately be measured, is a poor indicator of the resistance generated in response to immunization. Not only does it grow relatively slowly in the tissues of the nonimmune host, but it is also discouragingly resistant to inactivation, even at the height of the immunity generated during infection. Second, the challenge infection itself provokes an immune response which may be prompt and large enough to overshadow most of the effects of prior immunization. As a result, the observed differences between nonimmune and immunized animals are often small, regardless of whether they are estimated by bacterial enumeration or mortality data (1). These problems can be largely circumvented by using organisms other than the tubercle bacillus to measure the progressive changes in host resistance produced by vaccination with BCG. This approach is made feasible by the very high order of cross-resistance which develops between infections caused by intracellular bacterial parasites. This phenomenon of cross-resistance is dependent upon the well documented observation that when the mononuclear phagocytes of the infected host become highly resistant to infection their activities are not exclusively directed against the infective agent which induced the cellular change (2). In the present studies, Listerla monocytogenes and Salmonella lypkimuriura have been used to measure the development of host resistance after primary BCG infection in the mouse and to study the effect of reinfection with BCG.