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Published on: January 15, 2011
Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells
Adam D Judge1, Xiaohong Zhang, Hideki Fujii
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Insights
Memory T cells show mixed dependence on interleukin-15 (IL-15). Some CD8(+) T cell subsets require IL-15 for proliferation and survival, while others do not.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Previous research identified interleukin-15 (IL-15) as a key regulator of memory-phenotype CD44(hi) CD8(+) T cells.
- The precise extent of IL-15 dependency for these T cells remained incompletely understood.
Purpose of the Study:
- To investigate the heterogeneity of IL-15 dependency within memory-phenotype CD44(hi) CD8(+) T cell populations.
- To delineate distinct subsets of CD44(hi) CD8(+) T cells based on their IL-15 sensitivity.
Main Methods:
- Flow cytometry analysis of CD44, CD8, CD122, and Ly49 expression on T cells.
- Assessment of T cell proliferation, survival, and bystander proliferation under varying IL-15 conditions.
Main Results:
- CD44(hi) CD8(+) T cells are a mixed population with both IL-15-dependent and IL-15-independent subsets.
- The CD122(hi) CD44(hi) CD8(+) T cell subset, particularly Ly49(+) cells, exhibits strong IL-15 dependency for proliferation and survival.
- CD122(lo) CD44(hi) CD8(+) and CD44(hi) CD4(+) T cells are largely IL-15 independent.
Conclusions:
- Memory T cell subsets display significant variability in their requirement for IL-15.
- Differential IL-15 sensitivity among T cell subsets has implications for immune regulation and response.
Abstract:
Previous work has shown that memory-phenotype CD44(hi) CD8(+) cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44(hi) CD8(+) cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells. The major subset of CD122(hi) CD44(hi) CD8(+) cells is heavily dependent on IL-15 by three different parameters, namely (1) "bystander" proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal "background" proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49(+) subset of CD122(hi) CD44(hi) CD8(+) cells. In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.
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