Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection
- 10 July 2007
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (28), 11730-11735
- https://doi.org/10.1073/pnas.0705007104
Abstract
During many acute viral and bacterial infections, IL-7 receptor alpha-chain (IL-7Ralpha) is expressed on a subset of effector CD8 T cells that preferentially develop into long-lived memory CD8 T cells. These cells functionally require IL-7Ralpha, but it is unclear whether IL-7Ralpha acts mainly to induce their differentiation into memory cells or to sustain their long-term survival. To examine this question, IL-7Ralpha was constitutively overexpressed on all antigen-specific effector CD8 T cells during viral infection. Constitutive IL-7Ralpha expression had minimal effects on the numbers or function of effector and memory CD8 T cells formed. This indicated that IL-7Ralpha expression is not sufficient to drive memory cell development. In particular, the forced IL-7Ralpha expression did not rescue the killer cell lectin-like receptor G1 (KLRG1)(hi) short-lived effector CD8 T cells from death, showing that the majority of effector CD8 T cells die in an IL-7Ralpha-independent manner. Moreover, we found that, regardless of the ectopic expression of IL-7Ralpha, the KLRG1(hi), but not the KLRG1(lo) effector CD8 T cells, were unable to proliferate well to IL-7, which may be due to increased amounts of p27(kip) in KLRG1(hi) cells. Because IL-7 can destabilize p27(kip), this result suggested that KLRG1(hi) and KLRG1(lo) effector CD8 T cells naturally differ in their ability to transmit IL-7 signals. Altogether, these results reveal that IL-7Ralpha expression is permissive, but not instructive, to the creation of memory CD8 T cells.This publication has 36 references indexed in Scilit:
- Gene regulatory networks and the determination of lymphoid cell fatesCurrent Opinion in Immunology, 2006
- Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activationEuropean Journal of Immunology, 2006
- Regulation of mature T cell homeostasisSeminars in Immunology, 2005
- Inverse correlation between IL‐7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulationEuropean Journal of Immunology, 2005
- Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1Nature, 2003
- Role of the Intronic Enhancer in Tumor Necrosis Factor-mediated Induction of Manganous Superoxide DismutaseOnline Journal of Public Health Informatics, 2003
- Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T CellsThe Journal of Experimental Medicine, 2002
- Effector and memory T-cell differentiation: implications for vaccine developmentNature Reviews Immunology, 2002
- CD8+ T Cell Effector Mechanisms in Resistance to InfectionAnnual Review of Immunology, 2000
- Immunological Memory and Protective Immunity: Understanding Their RelationScience, 1996