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

tel-00827710, version 1 - 29 May 2013
2011). Finally, a study using the reporter mouse strain Ifnγ-YFP, which allows for the
visualization and detection of cells that express IFNγ show that even at the first cell division,
there exists already a high degree of variation in the expression of IFNγ on a per cell basis.
This suggests that a T cell is part of a fixed lineage and that its fate is imposed before the first
division (Beuneu et al., 2010).
D. T cell contraction and memory T cell formation
Following successful pathogen or antigen clearance, many effector T cells will die in order to
reestablish homeostatic, steady state levels of circulating immune cells.
1) T cell apoptosis during contraction
As part of this contraction phase, most of the effector cells will undergo apoptotic cell death.
This mechanism occurs through two distinct pathways (Strasser, 2005): (i) the extrinsic
pathway defined by TNF Receptor family engagement by their cognate ligands (TNFα, Fas,
TRAIL), or (ii) the intrinsic pathway, which is mediated by the disruption of the
mitochondrial membrane due to cellular stress and the release of components into the
cytoplasm. Signaling through both pathways results in the activation of Caspase 3 and 7 and
eventual apoptotic cell death. Yet, a small subset of effector cells survives this extreme
population contraction and these are the cells that constitute the memory T cell pool.
2) Conversion to memory T cells
(a) Metabolic switch
The T cells that survive to contraction will return to a resting quiescent state by switching
back to a catabolic metabolism, which allows for cell survival following the growth factor
withdrawal during the contraction phase. For example mTOR is a regulator of cell
metabolism integrating signals from microenvironment and its inhibtion by rapamycin
treatment promotes differentiation of effector T cells into memory cells (Araki et al., 2009).
Physiologically one could imagine that following antigen clearance, the microenvironment is
poor in nutrients and growth factors used up during the expansion phase, and that it would be
beneficial for this environment to favors the differentiation of memory T cells.
(b) Subsets of memory cells
All memory cells share the same stem cell-like phenotype. Memory cells are characterized by
their long life, in that they persist for long time even in the absence of antigen. During their
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