| CD8+ T-cells are a population of lymphocytes that mediate cytotoxic activity against transformed and virally infected cells. IL-15 is a pleiotropic cytokine involved in diverse aspects of CD8 + T-cell function. Among cytokines, IL-15 is unique since it is coordinately expressed on the cell surface with the IL-15Ralpha chain and presented in trans to opposing cells. Using cell-sized microspheres, the specific contribution of transpresented IL-15 to CD8+ T-cell binding, homeostasis and reactivation was examined.;The lack of defined phenotypic markers for memory CD8+ T-cells remains a major obstacle. Currently, no single marker can be used to identify memory CD8+ T-cells since many memory markers are commonly expressed by lymphocyte populations in various stages of differentiation. For this reason, the reactivity of a novel anti-Ly-6C mAb (iMap) developed in our laboratory was characterized. It was found that only high level expression of Ly-6C on CD8+ T-cells correlated with a functional memory phenotype. Importantly, iMap did not react with Ly-6C expressed on resting CD4+ T-cells as detected by another anti-Ly-6C mAb AL-21. Due to its restricted expression pattern, high iMap reactivity could be used a single marker to identify and isolate functional memory CD8+ T-cells from the secondary lymphoid organs.;Transpresented IL-15 has a rapid and profound effect on the binding and aggregation of CD8+ T-cells, particularily the central memory (TCM) subset. Live-cell imaging highlighted the adhesive properties of transpresented IL-15, which resembled "tethered" adhesion mediated by surface-bound chemokines. Functionally, transpresented IL-15 in the absence of any additional signals could maintain the long-term survival and antigen-specificity of lymphocytic choriomeningitis virus specific CD8+ T-cells in vitro . The capacity of IL-15 to reactivate memory CD8+ T-cells was next examined. It was found that transpresented IL-15 is required for optimal recall responses by memory CD8+ T-cells. In pursuing this further, TCM CD8+ T-cells were found to be more responsive to transpresented IL-15 than effector memory (TEM) CD8+ T-cells both in vitro and in vivo. Therefore, in addition to its well known role as a pro-survival cytokine, transpresented IL-15 functions as an adhesion molecule and as a memory CD8+ T-cell specific costimulatory ligand. |
