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Migratory properties of naive, effector, and memory CD8(+) T cells
W Weninger1, M A Crowley, N Manjunath
1The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
The Journal of Experimental Medicine
|October 3, 2001
Summary
Two CD8(+) T cell subsets show distinct migration patterns. Interleukin-15 (IL-15) cultured cells home to lymphoid organs, while IL-2 cultured cells target inflamed tissues for potent effector functions.
Area of Science:
- Immunology
- Cell Biology
- T cell differentiation
Background:
- Antigen-experienced T cells differentiate into subsets with distinct homing properties.
- Central memory T cells preferentially home to lymphoid organs, while effector memory T cells target non-lymphoid tissues.
- Murine CD8(+) T cells cultured in IL-15 (CD8(IL-15)) mimic central memory cells, whereas those cultured in IL-2 (CD8(IL-2)) become cytotoxic effector cells.
Purpose of the Study:
- To investigate and compare the migratory behavior of CD8(IL-15) and CD8(IL-2) T cell subsets.
- To determine the lymphoid and non-lymphoid tissue homing capabilities of these distinct T cell populations.
- To elucidate the molecular mechanisms governing T cell subset migration.
Main Methods:
- Intravital microscopy of peripheral lymph nodes (LNs).
- Analysis of T cell localization in spleen, LNs, and Peyer's patches.
- Assessment of T cell migration to sites of inflammation (peritoneum).
- Investigation of the roles of L-selectin and CC chemokine receptor 7 (CCR7) in migration.
Main Results:
- Naive and CD8(IL-15) cells localized to lymphoid organs (spleen T cell areas, LNs, Peyer's patches).
- CD8(IL-15) cells exhibited rolling and arrest in high endothelial venules (HEVs) in LNs, dependent on L-selectin and CCR7 ligands.
- Both CD8(+) subsets responded to inflammatory chemokines, but CD8(IL-2) cells were significantly more efficient (12-fold) at migrating to inflamed peritoneum.
- CD8(IL-15) cells showed rapid proliferation upon antigen reencounter at inflammatory sites.
Conclusions:
- CD8(IL-15) cells, resembling central memory T cells, efficiently home to lymphoid organs and exhibit moderate accumulation at inflammatory sites, mediating rapid recall responses.
- CD8(IL-2) cells, acting as effector T cells, preferentially accumulate in inflamed tissues but are largely excluded from lymphoid organs.
- Distinct cytokine-driven differentiation pathways (IL-15 vs. IL-2) dictate differential T cell homing and functional responses critical for adaptive immunity.
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