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The Journal of Immunology, 2001, 167: 5620-5627.
Copyright © 2001 by The American Association of Immunologists

Role of CD28 for the Generation and Expansion of Antigen-Specific CD8+ T Lymphocytes During Infection with Listeria monocytogenes1

Hans-Willi Mittrücker2,3, Mischo Kursar2, Anne Köhler, Robert Hurwitz and Stefan H. E. Kaufmann

Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany

Infection of mice with the intracellular bacterium Listeria monocytogenes results in a strong CD8+ T cell response that is critical for efficient control of infection. We used CD28-deficient mice to characterize the function of CD28 during Listeria infection, with a main emphasis on Listeria-specific CD8+ T cells. Frequencies and effector functions of these T cells were determined using MHC class I tetramers, single cell IFN-{gamma} production and Listeria-specific cytotoxicity. During primary Listeria infection of CD28-/- mice we observed significantly reduced numbers of Listeria-specific CD8+ T cells and only marginal levels of specific IFN-{gamma} production and cytotoxicity. Although frequencies were also reduced in CD28-/- mice during secondary response, we detected a considerable population of Listeria-specific CD8+ T cells in these mice. In parallel, IFN-{gamma} production and cytotoxicity were observed, revealing that Listeria-specific CD8+ T cells in CD28-/- mice expressed normal effector functions. Consistent with their impaired CD8+ T cell activation, CD28-/- mice suffered from exacerbated listeriosis both after primary and secondary infection. These results demonstrate participation of CD28 signaling in the generation and expansion of Ag-specific CD8+ T cells in listeriosis. However, Ag-specific CD8+ T cells generated in the absence of CD28 differentiated into normal effector and memory T cells.




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