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

tel-00827710, version 1 - 29 May 2013
Figure 36. Administration of K b -SIINFEKL antibody does not impact IFNγ production after i.d.
immunization. (A,B) Mice were immunized i.d. with 5x10 5 K bm1 mOva splenocytes. They received
anti-K b -SIINFEKL antibody or isotype control on days 7, 8 and 9. On day 10, the spleen and lymph
nodes were harvested for tetramer-based enrichment followed by ex vivo restimulation and
intracellular staining for IFNγ. (A) Representative FACS plots of CD8 + T cells were shown.
Percentages of CD8 + T cells making IFNγ were evaluated (B). (C) To test the ability of the antibody to
block antigen presentation, mice were immunized i.v. with 5x10 5 K bm1 mOva splenocytes. On day 2,
they received the blocking antibody or the isotype control. On day 3 post-immunization, 5x10 6
CD45.1 CFSE-labeled OT-I were transferred and the CFSE dilution was evaluated 3 days later.
In this section we demonstrated that the quality of the T cell response depends on the route of
immunization. As expected, systemically disseminated antigen resulted in rapid cross-
presentation, which correlated with the early differentiation of antigen-specific effector T
cells. This was in contrast to locally administered antigen, which showed delayed cross-
presentation and expansion of responding T cells. Although initially delayed, the T cell
response upon i.d. injection was much more robust and polyfunctional that that seen
following i.v. injection. Interestingly, the magnitude of T cell expansion was similar for both
routes of immunization. Thus, we can conclude that the route of immunization impacts T cell
quality but not primary expansion. These differences were not observed upon transfer of large
numbers of TCR-transgenic T cells, which highlights the importance of the in-depth
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