Lymphocyte Recruitment and Protective Efficacy against Pulmonary Mycobacterial Infection Are Independent of the Route of PriorMycobacterium bovisBCG Immunization

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Abstract
Mycobacterium tuberculosisinfects humans through the lung, and immunity to this chronic infection is mediated primarily by CD4+T lymphocytes. Recently we have demonstrated that the recruitment of lymphocytes to the lung during primary aerosolM. tuberculosisinfection in mice occurs predominantly through the interaction of α4β1integrin on CD4+T cells and vascular cell adhesion molecule-1 on the pulmonary endothelium. To investigate the effect of route of immunization withMycobacterium bovisBCG on the pattern of T-cell recruitment to the lung, we have analyzed the differences in expression of integrins on activated memory CD4+T cells infiltrating the lung following primary BCG immunization by aerosol, intravenous, and subcutaneous routes and after subsequent aerosol challenge withM. tuberculosis. There were marked differences in the patterns of recruitment of activated CD4+T cells to the lung following primary immunization by the three routes. Expansion of CD44hiCD62LlowCD4+T cells in the lung occurred following aerosol and intravenous BCG immunizations, and the lymphocyte recruitment was proportional to the pulmonary bacterial load. The majority of infiltrating CD4+T cells expressed α4β1integrin. On subsequent exposure to aerosol BCG rapid expansion of gamma interferon-secreting α4β1+CD4+T cells occurred to the same extent in all immunized mice, regardless of the route of immunization. Similar expansion of α4β1+CD4+memory T cells occurred followingM. tuberculosischallenge. The three routes of BCG immunization resulted in the same level of protection against aerosolM. tuberculosisor BCG challenge in both the lungs and spleen. Therefore, recruitment of effector T lymphocytes and protective efficacy against pulmonary mycobacterial infection are independent of the route of prior BCG immunization.