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CD8+ T cell-mediated protection against an intracellular bacterium by perforin-dependent cytotoxicity
1Institute of Experimental Immunology, Department of Pathology, University of Zürich, Switzerland.
Abstract:
Growth of Listeria monocytogenes is mainly controlled by macrophages, which are activated by specific T cells. A potential role of CD8+ T cells by direct lysis of infected cells was investigated in perforin-deficient mice generated by homologous recombination. The absence of perforin-mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after primary infection, overall susceptibility to Listeria however was not increased. Protection against a secondary infection was drastically impaired in perforin-deficient mice. Adoptive transfer of immune spleen cells to recipients revealed that anti-Listeria protection by CD8+ T cells from perforin-deficient versus normal mice was about 10-fold reduced in livers and about 100-fold reduced in the spleen of recipients. CD4+ T cells from immune control and perforin-deficient mice conferred comparable protection. These results indicate that the protective effect of CD8+ T cells against an intracellular bacterium mainly evident in secondary infection is mediated by a perforin-dependent pathway, presumably cytotoxicity, and less by other direct or indirect effector mechanisms.
Insights
Perforin-deficient mice showed impaired Listeria clearance, especially during secondary infections. CD8+ T cell protection against Listeria relies heavily on perforin-dependent cytotoxicity, crucial for controlling intracellular bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Listeria monocytogenes infection is primarily controlled by T cell-activated macrophages.
- The role of CD8+ T cells in directly lysing infected cells during Listeria infection is not fully understood.
Purpose of the Study:
- To investigate the role of perforin-mediated cytotoxicity by CD8+ T cells in controlling Listeria monocytogenes infection.
- To determine the contribution of CD8+ T cells to primary and secondary anti-Listeria immunity.
Main Methods:
- Generation of perforin-deficient mice using homologous recombination.
- Assessment of Listeria clearance in spleen and liver after primary infection.
- Evaluation of protection against secondary Listeria infection.
- Adoptive transfer of immune spleen cells (CD8+ T cells and CD4+ T cells) to assess anti-Listeria protection.
Main Results:
- Perforin deficiency caused delayed Listeria clearance from the spleen after primary infection, but overall susceptibility was not increased.
- Protection against secondary Listeria infection was significantly impaired in perforin-deficient mice.
- CD8+ T cells from perforin-deficient mice conferred substantially reduced protection compared to normal mice, particularly in the spleen.
- CD4+ T cells provided comparable protection regardless of perforin deficiency.
Conclusions:
- CD8+ T cell-mediated protection against Listeria, especially during secondary infections, is primarily dependent on perforin-mediated cytotoxicity.
- Other effector mechanisms of CD8+ T cells play a lesser role in controlling intracellular bacterial infections.