Expression of IL-7 receptor alpha 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-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.
Hand
Timothy W
TW
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Morre
Michel
M
Kaech
Susan M
SM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology*; D007156:Immunologic Memory; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D014615:Vaccinia / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain