Project Details
Description
Abstract
Memory CD8+ T cells are essential adaptive effector cells of immune defenses because they are extremely
efficient at sensing intracellular pathogens and tumors. The chief effector feature of CD8+ T cells is their ability
to recognize and kill infected and “abnormal” cells but they also produce multiple effector cytokines and
chemokines that contribute to orchestrate protective immune responses. The cellular and molecular stepwise
mechanisms by which memory CD8+ T cells in vaccinated hosts are reactivated and mediate protection is not
well understood. Answering to this question has the potential to lead to novel strategies to harness or redirect
the power of CD8+ T cells to the benefit of the host in many therapeutic contexts. Over the years, using mice
immunized with the intracellular bacterium Listeria monocytogenes (Lm) as model, we have contributed to
show that during recall infection, vaccine-induced memory CD8+ T cells quickly sense sets of inflammatory
cytokines released from various antigen-presenting cells (APCs), which initiate a rapid effector program in the
memory CD8+ T cells. This includes notably the secretion of the potent immunomodulatory cytokine IFN which
further signals and activates microbicidal functions inside phagocytes, a necessary process for efficient
protection of vaccinated hosts. Yet, IFN is secreted to similar extent whether cognate T cell antigens are
present or not. Protection, however, is antigen-specific, suggesting that other factors distinct from memory
CD8+ T cell-derived IFN account for IFN-mediated protection. This proposal investigates these factors and
their regulation in the memory CD8+ T cells, which APCs provide cognate antigen to the memory CD8+ T cells
during recall infection and the dynamic interactions of memory CD8+ T cells and killer phagocytes using
cutting-edge intravital imaging approaches. Finally, we will also dissect the mechanisms of IFN-dependent
cell-autonomous defenses that are triggered inside activated phagocytes. We predict successful completion of
the proposed work will have a broad impact in the field of T cell biology and vaccines, and potentially important
therapeutic implications.
Status | Finished |
---|---|
Effective start/end date | 12/15/12 → 7/31/23 |
Funding
- National Institute of Allergy and Infectious Diseases: $8,049.00
- National Institute of Allergy and Infectious Diseases: $258,228.00
- National Institute of Allergy and Infectious Diseases: $602,572.00
- National Institute of Allergy and Infectious Diseases: $377,794.00
- National Institute of Allergy and Infectious Diseases: $313,125.00
- National Institute of Allergy and Infectious Diseases: $417,500.00
- National Institute of Allergy and Infectious Diseases: $584,868.00
- National Institute of Allergy and Infectious Diseases: $104,375.00
- National Institute of Allergy and Infectious Diseases: $89,584.00
- National Institute of Allergy and Infectious Diseases: $392,450.00
- National Institute of Allergy and Infectious Diseases: $417,500.00
- National Institute of Allergy and Infectious Diseases: $417,500.00
- National Institute of Allergy and Infectious Diseases: $566,443.00
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