Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection

Jul 5, 2007Proceedings of the National Academy of Sciences of the United States of America

IL-7 receptor alpha is required but alone not enough for memory CD8 T cell formation during viral infection

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Abstract

IL-7 receptor alpha-chain (IL-7Ralpha) expression is not sufficient to drive the development of memory CD8 T cells during viral infection.

IL-7Ralpha is expressed on a subset of effector CD8 T cells that can develop into long-lived memory cells.
Constitutive overexpression of IL-7Ralpha did not significantly change the numbers or functions of effector and memory CD8 T cells.
Most effector CD8 T cells, particularly those marked by high levels of KLRG1, die independently of IL-7Ralpha.
KLRG1(hi) effector CD8 T cells show reduced proliferation in response to IL-7, potentially due to higher levels of the protein p27(kip).
KLRG1(hi) and KLRG1(lo) effector CD8 T cells exhibit differences in their ability to respond to IL-7 signaling.

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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.

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Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection

Abstract

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