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The Journal of Immunology, Vol 156, Issue 9 3321-3326, Copyright © 1996 by American Association of Immunologists
ARTICLES |
J Hess, C Ladel, D Miko and SH Kaufmann
Department of Immunology, University of Ulm, Germany.
Due to the dependency on aromatic precursors, the growth of Salmonella typhimurium aroA- is limited in immunocompetent mice. Here we show that H-21-A beta-/- mice (lacking MHC class II molecules and thus devoid of mature CD4+ TCR-alpha beta cells), TCR-beta-/- mice (devoid of TCR- alpha beta cells), and IFN-gamma R-/- mice (unresponsive to IFN-gamma) are highly susceptible to S. typhimurium aroA- infection compared with heterozygous controls. In contrast, beta 2m-deficient mice (lacking surface MHC class I and thus devoid of conventional CD8+ T cells) or TCR-delta-/- mice (devoid of TCR-gamma delta cells) were equally as resistant to S. typhimurium aroA- infection as their heterozygous littermates. These findings emphasize the vital role of CD4+ TCR-alpha beta cells and IFN-gamma in resistance against S. typhimurium aroA-. Sublethal inocula of S. typhimurium aroA- led to permanent infection in H-21-A beta-/- mice, suggesting that bacterial starvation is insufficient for sterile clearance in immunocompetent mice and that MHC class II-dependent immune mechanisms are required for pathogen eradication. The TCR-beta-/- mice suffered from salmonellosis more severely than the MHC class II-deficient mutants, suggesting an auxiliary function of CD8+ T cells. Recombinant S. typhimurium aroA-, secreting listeriolysin (Hly) of Listeria monocytogenes, are capable of escaping from the phagosome into the cytosol of the host cell. However, the course of infection of these recombinant S. typhimurium SL7207 Hlys and control strains did not differ in beta 2m-/- mutants. This finding argues against direct correlation of cytosolic location of S. typhimurium SL7207 Hlys with CD8+ T cell dependency of protection.
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H.-W. Mittrucker, B. Raupach, A. Kohler, and S. H. E. Kaufmann Cutting Edge: Role of B Lymphocytes in Protective Immunity Against Salmonella typhimurium Infection J. Immunol., February 15, 2000; 164(4): 1648 - 1652. [Abstract] [Full Text] [PDF]
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H.-W. Mittrucker, A. Kohler, T. W. Mak, and S. H. E. Kaufmann Critical Role of CD28 in Protective Immunity Against Salmonella typhimurium J. Immunol., December 15, 1999; 163(12): 6769 - 6776. [Abstract] [Full Text] [PDF]
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P. Mastroeni, J. A. Harrison, J. H. Robinson, S. Clare, S. Khan, D. J. Maskell, G. Dougan, and C. E. Hormaeche Interleukin-12 Is Required for Control of the Growth of Attenuated Aromatic-Compound-Dependent Salmonellae in BALB/c Mice: Role of Gamma Interferon and Macrophage Activation Infect. Immun., October 1, 1998; 66(10): 4767 - 4776. [Abstract] [Full Text] [PDF]
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P. Everest, M. Roberts, and G. Dougan Susceptibility to Salmonella typhimurium Infection and Effectiveness of Vaccination in Mice Deficient in the Tumor Necrosis Factor Alpha p55 Receptor Infect. Immun., July 1, 1998; 66(7): 3355 - 3364. [Abstract] [Full Text] [PDF]
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G. Geginat, M. Lalic, M. Kretschmar, W. Goebel, H. Hof, D. Palm, and A. Bubert Th1 Cells Specific for a Secreted Protein of Listeria monocytogenes Are Protective In Vivo J. Immunol., June 15, 1998; 160(12): 6046 - 6055. [Abstract] [Full Text] [PDF]
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