Memory CD44(int) CD8 T cells show increased proliferative responses and IFN-gamma production following antigenic challenge in vitro

F5 TCR transgenic mice challenged in vivo with peptide generate long-lived primed CD8 T cells that hyper-proliferate in response to peptide in vitro. These primed CD8 T cells can be subdivided into three distinct populations on the basis of CD44 cell surface expression. In this report, we show that among primed CD8 T cells, those expressing intermediate levels of CD44 appe ar to be true memory T cells by the measurement of a variety of characteris tics. Indeed, these cells hyperproliferate in response to peptide re-stimul ation in vitro, and produce IFN-gamma with faster kinetics and at higher le vels than naive populations in vitro. We also show that CD8 T cells express ing high levels of CD44 express several activation markers and cycle in viv o in the absence of antigen. However, this population is unable to respond to peptide stimulation in vitro as measured by both proliferation and IFN-g amma secretion. The origin and specificity of these cells is unknown, These results provide evidence that memory CD8 T cells are functionally differen t from naive CD8 T cells both in terms of proliferation and cytokine secret ion. They identify the CD8/CD44(int) T cells as the population responsible for hyper-reactivity in vitro.