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

During many acute viral and bacterial infections, IL-7 receptor alpha-chain (IL-7R alpha) 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-7R alpha, but it is unclear whether IL-7R alpha acts mainly to induce their differentiation into memory cells or to sustain their long-term survival. To examine this question, IL-7R alpha was constitutively overexpressed on all antigen-specific effector CD8 T cells during viral infection. Constitutive IL-7R alpha expression had minimal effects on the numbers or function of effector and memory CD8 T cells formed. This indicated that IL-7R alpha expression is not sufficient to drive memory cell development. In particular, the forced IL-7R alpha 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-7R alpha-independent manner. Moreover, we found that, regardless of the ectopic expression of IL-7R alpha, the KLIRG1(hi), but not the KLRG1(10) effector CD8 T cells, were unable to proliferate well to IL-7, which may be due to increased amounts of p27(kip) in KLIRG1(hi) cells. Because IL-7 can destabilize p27(kip), this result suggested that KILRG1(hi) and KLRG1(lo) effector CD8 T cells naturally differ in their ability to transmit IL-7 signals. Altogether, these results reveal that IL-7R alpha expression is permissive, but not instructive, to the creation of memory CD8 T cells.