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The Journal of Immunology, 1974, 112: 1322-1328.
Copyright © 1974 by The American Association of Immunologists, Inc.
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Local and Systemic Cell-Mediated Immunity after Immunization of Guinea Pigs with Live or Killed M. Tuberculosis by Various Routes1

James C. Spencer, Robert H. Waldman2 and Joseph E. Johnson, III3

From the Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida 32610 and Veterans Administration Hospital, Gainesville, Florida 32602

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.

Footnotes

1 This research was conducted in facilities accredited by the American Association of Laboratory Animal Care, and was supported by The National Institutes of Health Training Grant AI 00341, National Institutes of Health Research Grant AI 10295, and Florida Division of the American Cancer Society Grant F-73UF-2.

2 Recipient of National Institutes of Health Research Career Development Award AI 36631.

3 Present Address: Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.






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