Abstracts (complete list) - Wissenschaft Online

Christian Stemberger, Katharina Huster, Martina Koffler, Florian Anderl, Matthias
Schiemann, Hermann Wagner, Dirk Busch
Heterogeneous subset generation from a single naïve CD8+ T
cell upon in vivo priming
CD8+ T cells are crucial for protection against intracellular pathogens and some tumors.
Upon first encounter with their cognate antigen, naïve T cells get activated (‘primed’),
clonally expand, and can develop into very distinct subsets. These comprise short-living
effector T cells that confer immediate protection by different types of effector functions,
and memory T cell subsets such as effector- and central memory T cells. Because these
subsets contribute differently to protective immunity and therefore have different
implications for the development of vaccination strategies, it is of outstanding interest
to understand how subset diversity is generated. However, so far it has only been
possible to tackle questions regarding the origin of diversification via analysis of indirect
parameters, such as TCR repertoires, and these experiments were limited to global
analyses of clonotypic T cells.
To improve analysis of T cell subset generation on a cellular level in vivo, we developed
a novel adoptive transfer system that allows for the first time to trace the fate of a
single antigen-specific naïve T cell in a normal (wild-type) recipient mouse. Upon
immunization, clonal expansion and differentiation of single cell-derived daughter cells
was monitored in a natural in vivo setting. Phenotypical and functional analyses of
“single cell”-expanded populations demonstrated that a wide range of diversity can
develop out of a single naïve precursor cell, including different types of effector cells
and long-living memory T cell subsets. Most interestingly, we uncovered that subset
diversification derived from a single cell strictly reflects the differentiation pattern found
for the endogenous repertoire (in the same individual mouse). This finding indicate that
the origin of subset diversification lies primarily in the intrinsic plasticity within clonal
precursors, or in differences in the range of signals provided to their progeny at stages
during expansion going far beyond the first cell division.