Role of CD28 for the generation and expansion of antigen-specific CD8(+) T lymphocytes during infection with Listeria monocytogenes.
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.
Mittrücker
H W
HW
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. mittruecker@mpiib-berlin.mpg.de
Kursar
M
M
Köhler
A
A
Hurwitz
R
R
Kaufmann
S H
SH
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000942:Antigens, Bacterial; D018106:CD28 Antigens; D007376:Interleukin-2; D010455:Peptides; D007371:Interferon-gamma