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

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.

• Authors: Timothy W Hand, Michel Morre, Susan M Kaech
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 28 Pg. 11730-5 (Jul 10 2007) ISSN: 0027-8424 [Print] United States
• PMID: 17609371 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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