Studies of Tubercle Bacillus-Histiocyte Relationships

Abstract

Earlier reports (1, 2) from this laboratory have shown that immunization of animals with the BCG strain of tubercle bacillus resulted in the development of resistant populations of histiocytes in these animals; this form of cellular resistance was manifested by the refractoriness of infected immune histiocytes to necrotization by virulent tubercle bacilli (H37Rv strain). The expression of such resistance was, however, dependent upon the presence of some non-specific factor present in homologous and heterologous immune sera (e.g. anti-BCG, antiovalbumin, anti-Salmonella sera).Further studies (3) have shown that a similar type of cellular resistance was demonstrable with the histiocytes of rabbits immunized with the Rev I strain of Brucella mel/tens/s. There was, moreover, a state of cross-immunity between the Brucella-immune (from animals immunized with Rev I) and the BCG-immune (from animals immunized with BCG) histiocytes such that infection of one or the other of the two histiocytes with either the homologous or heterologous pathogen did not result in destruction of cells by the parasite. An obvious inference which may be drawn from this observation is the probable identity of the mechanism or mechanisms for this type of cellular resistance.Since the above findings have been reported, additional characterization of the tubercle bacillus-histiocyte model system has been achieved (4--6). It is now known that cellular resistance against mycobacteria can be induced in normal animals by injections of immune histiocytes, recipient histiocytes (histiocytes of normal animals which had been injected with resistant cells), and by immune ribosomes and ribosomal RNA (ribonucleic acid). It is also an established fact that serial transfer of resistance in normal animals against mycobacteria is achievable by injection of animals with resistant histiocytes or subfractions (ribosomes) derived therefrom. Moreover, it has been shown that passage of virulent tubercle bacilli in immune histiocytes resulted in attenuation of bacilli for both mice and normal histiocytes (i.e. passaged bacilli lose their inherent ability to necrotize the histiocytes of normal animals).In view of the above findings, it seemed propitious to investigate the identity or lack of identity of the basic mechanisms which underlie cellular immunity