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CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow
Elisabetta Parretta1, Giuliana Cassese, Pasquale Barba
1Institute of Genetics and Biophysics, Adriano Buzzati Traverso, Consiglio Nazionale delle Ricerche, Naples, Italy.
Journal of Immunology (Baltimore, Md. : 1950)
|June 10, 2005
Summary
The bone marrow is a key site for the sustained proliferation of memory CD8 T cells, crucial for long-term immunity against pathogens. These cells divide more in the bone marrow than in other organs, maintaining immunological memory.
Area of Science:
- Immunology
- Cell Biology
- T cell memory
Background:
- Long-term persistence of Ag-experienced CD8 T cells is vital for immunological memory against intracellular pathogens.
- Memory CD8 T cells are maintained by slow, cytokine-driven proliferation after antigen clearance.
Purpose of the Study:
- To identify the primary organ responsible for the basal division of memory CD8 T cells.
- To investigate the role of the bone marrow in maintaining cytotoxic T cell memory.
Main Methods:
- Comparison of proliferation rates of memory CD8 T cells in bone marrow versus spleen and lymph nodes in C57BL/6 mice.
- Analysis of Ag-specific memory CD8 T cells and memory-phenotype CD44high CD8 cells.
- Quantification of Ag-specific memory CD8 T cell numbers and division in various organs.
- Measurement of CD127 (IL-7R alpha-chain) expression on Ag-specific memory CD8 T cells in different tissues.
Main Results:
- The bone marrow harbors a higher percentage of proliferating memory CD8 T cells compared to spleen and lymph nodes.
- The absolute number of dividing Ag-specific memory CD8 T cells in the bone marrow significantly exceeds that in spleen, lymph nodes, liver, and lung combined.
- Ag-specific memory CD8 T cells in the bone marrow express lower levels of CD127 (IL-7R alpha-chain) than those in spleen or lymph nodes.
Conclusions:
- The bone marrow serves as a critical niche for the Ag-independent proliferation and maintenance of memory CD8 T cells.
- Proliferative signals, potentially from IL-7 and/or IL-15, are received by memory CD8 T cells within the bone marrow.
- The bone marrow plays a significant role in sustaining cytotoxic T cell memory, complementing its known role in long-term antibody responses.