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

tel-00827710, version 1 - 29 May 2013
Figure 13. Limit of detection of established techniques for studying the T cell response in vivo.
(d) Adoptive transfer of TCR-transgenic CD8 T cells
Some antigens induce a low level T cell response, which is not consistently detectable by the
techniques just described. Another approach was developed to study the T cells that are
specific for a given epitope, even in the case that the response is not robust. To address this
and develop a technique that would allow for these instances, mice that were transgenic for a
given TCR were generated. In these mice, the vast majority of the CD8 + T cells are specific
for the same epitope. These mice were then crossed to Rag-deficient mice, ensuring that all T
cells were specific for this epitope. In this way, various numbers of antigen-specific T cells
can be transferred into naïve mice, allowing for easier detection by artificially increasing the
precursor frequency. The transfer of TCR-transgenic T cells has been extensively used to
model the endogenous response in combination with tetramer and intracellular staining.
Another benefit of this approach is the possibility to label transgenic T cells prior to their
transfer in order to follow them in vivo. Moreover, it is also possible to transfer TCR-
transgenic T cells that are deleted for specific genes to further dissect the mechanisms of the T
cell response.
Some years ago, several groups demonstrated that adoptive transfer experiments using large
numbers of specific T cells can actually modify the outcome of the immune response under
examination (Marzo et al., 2005). It was then realized and acknowledged that the transfer of
non-physiologic numbers of TCR-transgenic T cells does not accurately mimic the
endogenous response, which poses a severe limitation on the interpretation of studies using
this strategy. Specifically, Badovinac and colleagues performed experiments transferring
graded numbers of TCR-transgenic T cells and showed that high initial precursor frequencies
actually limited the expansion of effector cells (Badovinac et al., 2007). They concluded that
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