RESTING MEMORY CD8(-CELLS ARE HYPERREACTIVE TO ANTIGENIC CHALLENGE IN-VITRO() T)

The characteristics of CD8(+) T cells responsible for memory responses are still largely unknown. Particularly, it has not been determined w hether different activation thresholds distinguish naive from memory C D8(+) T cell populations. In most experimental systems, heterogeneous populations of primed CD8(+) T cells can be identified in vivo after i mmunization. These cells differ in terms of cell cycle status, surface phenotype, and/or effector function. This heterogeneity has made it d ifficult to assess the activation threshold and the relative role of t hese subpopulations in memory responses. In this study ave have used F 5 T cell receptor transgenic mice to generate a homogeneous population of primed CD8(+) T cells. In the F5 transgenic mice, peptide injectio n in vivo leads to activation of most peripheral CD8(+) T cells. In vi vo BrdU labeling has been used to follow primed T cells over time peri ods spanning several weeks after peptide immunization. Our results sho w that the majority of primed CD8(+) T cells generated in this system are not cycling and express increased levels of CD44 and Ly6C. These c ells remain responsive to secondary peptide challenge in vivo as evide nced by short term upregulation of activation markers such as CD69 and CD44. The activation thresholds of naive and primed CD8(+) T cells we re compared in vitro. We found that CD8(+) T cells from primed mice ar e activated by peptide concentrations 10-50-fold lower than naive mice . In addition, the kinetics of interleukin 2R alpha chain upregulation by primed CD8(+) T cells differ from naive CD8(+) T cells. These prim ed hyperresponsive CD8(+) T cells might play an important role in the memory response.