Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
called signal 0, as it occurs prior to the critical T cell-DC encounter (Bousso and Albert,
2010).
C. T cell expansion and differentiation
Upon activation, T cells undergo proliferation and differentiation to form a diverse population
of cells with various functionalities and abilities to convert into memory cells.
1) Metabolic demands of activated T cells
Activated T cells increase in size and quickly divide up to 20 times. This requires significant
changes to their metabolism in order to support this high proliferation rate. Indeed naïve T
cells are in a quiescent state where catabolism is predominant. They use autophagy to
generate the molecules required for energy and basal protein synthesis. Upon activation, the
metabolic demand increases dramatically and the cells switch from catabolism to anabolism.
The cells now employ glycolysis to generate energy despite high amounts of oxygen. This
state of oxidative glycolysis is called the “Warburg effect” and has also been described for
cancer cells. ATP production by aerobic glycolysis is much less efficient than by oxidative
phosphorylation, but this metabolic pathway also allows for the generation of molecules to
build new cellular components (Pearce, 2010). That could be the explanation as to why T
cells use this pathway. Additionally, the cells increase their expression of nutrient
transporters. Together these changes facilitate the massive proliferation that is initiated
following T cell activation. Following the expansion phase, cellular metabolism returns again
to a quiescent state in memory cells.
2) Heterogeneity of the T cell population
Circulating T cells exist as a diverse, heterologous population. The parameters responsible for
the diversification are not yet known. However it is thought that the different quantitative and
qualitative signals received by the naïve T cell during the first steps of activation (signals 1, 2,
3) can significantly impact the diversity of the global T cell population. Additionally, the role
of the tissue microenvironment in promoting T cell diversity during the course of the immune
response remains to be completely understood.
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