Local and Systemic Cell-Mediated Immunity after Immunization of Guinea Pigs with Live or Killed M. Tuberculosis by Various Routes

Abstract

Abstract Recent studies have suggested that there is compartmentalization of the cell-mediated immune response, i.e., local (nasal) immunization with influenza virus vaccine is more effective in inducing local cell-mediated immunity (CMI) than is parenteral immunization, whereas parenteral immunization is more effective in inducing systemic immunity. This study was undertaken to investigate the development of local respiratory as compared to systemic CMI in response to both nasally and parenterally administered BCG or killed Mycobacterium tuberculosis H37Ra. CMI was tested with guinea pigs as the animal model and the inhibition of macrophage migration (IMM) technique at various intervals after immunization. Splenic lymphocytes were used as indicators of systemic immunity and pulmonary cells obtained by lung lavage were used to measure local immunity. The animals immunized via the respiratory tract with either H37Ra or BCG developed significantly greater local respiratory CMI (greater percentage of IMM) than did animals immunized subcutaneously although the parenterally immunized animals developed greater systemic immunity. This compartmentalization of CMI could be overcome partially with higher doses of H37Ra, i.e., both respiratory and systemic CMI resulted from high dose local or parenteral immunization. The response after BCG (live), as compared to H37Ra (killed organisms), was more prolonged: by 6 weeks after H37Ra immunization, by any route, there was no IMM; however, after BCG, high levels of IMM were present at 6 weeks. When guinea pigs were immunized i.v. with H37Ra, neither systemic nor respiratory CMI was stimulated. I.v. BCG stimulated systemic but not respiratory CMI. These results could not be explained on the basis of local immunization leading to local irritation and infiltration of lymphocytes into the lung, since cell counts and histologic studies revealed no difference between the animals immunized locally and systemically. These results may have implications with respect to immunization of humans against tuberculosis.