{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:57:43Z","timestamp":1779213463038,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":3942,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1995,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Knock\u2010out mice with defined major histocompatibility complex (MHC) deficiencies were infected intravenously with <jats:italic>Mycobacterium bovis<\/jats:italic> bacille Calmette Gu\u00e9rin (<jats:italic>M. bovis<\/jats:italic> BCG) to assess the relative impact of MHC class I\u2010 and II\u2010dependent immune responses. Heterozygous control mice were capable of controlling growth of <jats:italic>M. bovis<\/jats:italic> BCG, although infection progressed chronically, as assessed by determination of colony\u2010forming units. Furthermore, infected controls developed granulomatous lesions at the site of mycobacterial growth and delayed\u2010type hypersensitivity (DTH) reactions after challenge with purified protein derivative of tuberculin. <jats:italic>In vitro<\/jats:italic>, spleen cells from heterozygous control mice produced high concentrations of interferon\u2010\u03b3 (IFN\u2010\u03b3) after restimulation with mycobacterial antigens. In contrast, the MHC class II\u2010deficient A\u03b2<jats:sup>\u2212\/\u2212<\/jats:sup> mice, which are virtually devoid of functional CD4 T cells, succumbed to <jats:italic>M. bovis<\/jats:italic> BCG infection. Furthermore, A\u03b2<jats:sup>\u2212\/\u2212<\/jats:sup> mice lacked DTH reactions to tuberculin and only few minute picnotic lesions were formed in livers of infected mice. Finally, spleen cells from infected A\u03b2<jats:sup>\u2212\/\u2212<\/jats:sup> mice failed to produce measurable IFN\u2010\u03b3 concentrations after restimulation <jats:italic>in vitro<\/jats:italic> with various mycobacterial antigen preparations. The capacity of \u03b22\u2010microglobulin (\u03b22m)\u2010deficient mice, which are devoid of CD8\u03b1\/\u03b2 T cells, to inhibit growth of <jats:italic>M. bovis<\/jats:italic> BCG was only slightly affected at low inocula, although significantly higher colony\u2010forming units were detected in spleens. These knock\u2010out mice developed strong DTH responses to tuberculin and their spleen cells produced high levels of IFN\u2010\u03b3 once reactivated by mycobacterial antigens. Furthermore, in livers of infected \u03b22m\u2010deficient mice, extravascular infiltrates developed which were more diffuse than those in infected control littermates. Remarkably, the \u03b22m\u2010deficient mice were substantially more susceptible to higher inocula of <jats:italic>M. bovis<\/jats:italic> BCG than their control littermates. Our data formally prove the essential role of MHC class II\u2010dependent immune mechanisms in all relevant aspects of immunity to <jats:italic>M. bovis<\/jats:italic> BCG. In addition, our findings emphasize an important contribution of MHC class I\u2010dependent immunity to effective anti\u2010mycobacterial protection. We assume that CD4 T cells are highly effective in containing <jats:italic>M. bovis<\/jats:italic> BCG within distinct granulomatous lesions, but fail to eradicate their intracellular pathogens. It appears most likely that CD8 T cells are also required to achieve this goal.<\/jats:p>","DOI":"10.1002\/eji.1830250211","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T00:32:56Z","timestamp":1172795576000},"page":"377-384","source":"Crossref","is-referenced-by-count":168,"title":["Immune response to <i>Mycobacterium bovis<\/i> bacille Calmette Gu\u00e9rin infection in major histocompatibility complex class I\u2010 and II\u2010deficient knock\u2010out mice: contribution of CD4 and CD8 T cells to acquired resistance"],"prefix":"10.1002","volume":"25","author":[{"given":"Christoph H.","family":"Ladel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Daugelat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan H. 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