Overexpression of Interleukin (IL)-7 Leads to IL-15–independent Generation of Memory Phenotype CD8(+) T Cells

Transgenic (TG) mice expressing a high copy number of interleukin (IL)-7 cDNA under the control of the major histocomaptability complex (MHC) class II promoter display a 10–20-fold increase in total T cell numbers. Here, we show that the increase in T cell numbers in IL-7 TG mice is most apparent at the level of memory phenotype CD44(hi) CD122(hi) CD8(+) cells. Based on studies with T cell receptor (TCR) TG mice crossed to IL-7 TG mice, increased levels of IL-7 may provide costimulation for TCR recognition of self-MHC ligands and thus cause naive CD8(+) cells to proliferate and differentiate into memory phenotype cells. In addition, a marked increase in CD44(hi) CD122(hi) CD8(+) cells was found in IL-7 TG IL-15(−) mice. Since these cell are rare in normal IL-15(−) mice, the dependency of memory phenotype CD8(+) cells on IL-15 can be overcome by overexpression of IL-7.