T cell fate mapping and lineage tracing technologies probing clonal aspects underlying the generation of CD8 T cell subsets.

ABSTRACT

T cells responding to acute infections generally provide two key functions to protect the host (1) active contribution to pathogen elimination and (2) providing long-lived cells that are poised to rapidly respond to renewed infection, thus ensuring long-lasting protection against the particular pathogen. Extensive work has established an astonishing amount of additional diversity among T cells actively contributing to pathogen elimination, as well as among resting, long-lived antigen-experienced T cells. This led to the description of a variety of functionally distinct T cell 'subsets'. Understanding how this heterogeneity develops among T cells responding to the same antigen is currently an active area of research, since knowledge of such mechanisms may have implications for the development of vaccines and immunotherapy. The number of naïve T cells specific to a given antigen span a great range. Considering this, one mechanistic angle focusses on how individual naïve T cells contribute to the development of the distinct T cell subsets. In this review, we highlight the current technologies that enable one to address the contributions of individual naïve T cells to different T cell subsets, with a focus on CD8 T cell subsets generated in the context of acute infections. Moreover, we discuss the requirements of new technologies to further our understanding of the mechanisms that help generate long-lasting immunity.