Principles of memory CD8 T-cells generation in relation to protective immunity.

Memory T-cell responses are of vital importance in understanding the host's response against pathogens and cancer cells and to begin establishing the correlation of protection against disease. In this review, we discuss our own data in the general context of current knowledge to sketch tentative working principles for the induction of protective T-cell responses by vaccination. We draw attention to quantitative and qualitative aspects of the initial contact with antigen, as well as to the kinetics of events leading to the generation of memory T cells thereafter. Our arguments are based on the current distinction of memory T cells into two lineages: effector memory T cells (T(EM)) and central memory T cells (T(CM)). Our provisional conclusion is that protective T-cell responses correlate positively with the T cells of the central memory phenotype. In proposing a set of working principles to enable protective memory T cells by vaccination we address vaccination both in the context of the immunologically-inexperienced and immunologically-experienced individual, respectively. Finally, we draw attention to the interplay between systemic and local immunity as important factors in determining the success of memory T-cell responses in protecting the individual. We believe that considerations on the immunodynamics of memory induction and maintenance, memory lineage differentiation and their relation to protection may help design strategies to control disease caused by pathogens and cancer.