Open AccessExpression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection
Author(s) -
Timothy W. Hand,
Michel Morre,
Susan M. Kaech
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0705007104
Subject(s) - cytotoxic t cell , biology , effector , cd8 , microbiology and biotechnology , memory t cell , il 2 receptor , interleukin 21 , t cell , immunology , immune system , in vitro , genetics
During many acute viral and bacterial infections, IL-7 receptor α-chain (IL-7Rα) 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-7Rα, but it is unclear whether IL-7Rα acts mainly to induce their differentiation into memory cells or to sustain their long-term survival. To examine this question, IL-7Rα was constitutively overexpressed on all antigen-specific effector CD8 T cells during viral infection. Constitutive IL-7Rα expression had minimal effects on the numbers or function of effector and memory CD8 T cells formed. This indicated that IL-7Rα expression is not sufficient to drive memory cell development. In particular, the forced IL-7Rα 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-7Rα-independent manner. Moreover, we found that, regardless of the ectopic expression of IL-7Rα, the KLRG1hi , but not the KLRG1lo effector CD8 T cells, were unable to proliferate well to IL-7, which may be due to increased amounts of p27kip in KLRG1hi cells. Because IL-7 can destabilize p27kip , this result suggested that KLRG1hi and KLRG1lo effector CD8 T cells naturally differ in their ability to transmit IL-7 signals. Altogether, these results reveal that IL-7Rα expression is permissive, but not instructive, to the creation of memory CD8 T cells.