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

tel-00827710, version 1 - 29 May 2013
based immune suppression is important for avoiding autoimmune responses that could
develop as a side effect of inflammation. Unfortunately, these self-regulatory systems can also
be manipulated and inhibit an efficient immune response or therapeutic intervention; often
this occurs during cancer development, when the tumor itself promotes the action of
regulatory T cells, as well as the secretion of immunosuppressive cytokines such as TGFβ or
IL-10, which then limits the development of an anti-tumor CD8 + T cell response (Vanneman
and Dranoff, 2012).
III. HOW TO MODULATE CD8 + T CELL CROSS-PRIMING?
Understanding the basis of antigen cross-presentation and CD8 + T cell priming is essential to
be able to modulate the immune response and develop effective treatments against disease. As
previously mentioned, the majority of successful vaccines developed thus far trigger a
humoral, antibody-based response rather than cell-mediated immunity. However, in many
cases it is the CD8 + T cell immunity that has been shown to be critical for controlling diseases
for which efficient vaccines have not yet been developed, such as HIV, malaria or
tuberculosis (Rappuoli and Aderem, 2011). Cell-mediated immunity is also crucial to fight
cancer or chronic viral infections. Consequently, developing vaccines that trigger T cell
immunity will be absolutely required to improve current therapies for a wide range of
pathologies. To explore this concept further, I will review the possible ways to modulate
CD8 + T cell cross-priming: first, how different forms of antigen can be used to elicit various
T cell responses and second, the use of adjuvants, and especially type I IFN-inducers, to boost
an antigen-specific T cell response.
A. Stimulation of the immune response with diverse forms of
antigen
A variety of antigens can be used to induce an immune response. Each of them displays
particular characteristics regarding their uptake, processing, presentation by APCs and their
resulting immunogenicity. Depending on the desired immune response, the form of antigen
must be carefully chosen and, in some cases, additional reagents such as adjuvant should be
administered in parallel to attain maximal protective immunity (Table 5).
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