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

Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11730-5. doi: 10.1073/pnas.0705007104. Epub 2007 Jul 3.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology*
  • Cell Differentiation / immunology*
  • Immunologic Memory*
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Listeriosis / pathology
  • Lymphocyte Count
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / metabolism
  • Lymphocytic Choriomeningitis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Interleukin-7 / biosynthesis*
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / physiology
  • Vaccinia / immunology
  • Vaccinia / metabolism
  • Vaccinia / pathology


  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain