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Gasteiger, G. ; Kastenmüller, W. ; Stross, L.* ; Sparwasser, T.* ; Busch, D.H. ; Drexler, I.

Regulatory T cells limit effector but not memory T cell responses to vaccination.

Vortrag: International Meeting 2009, 30th August - 02nd September 2009, Tour, France. (2009)
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Chronically infected HBV and HCV patients develop regulatory T cells (Treg) that appear to prevent functional cytotoxic T cell responses. The hope that these patients could benefit from therapeutic vaccination is based on the observation that viral clearance during acute infection is correlated with a strong and multispecific T cell response. Viral vectors delivering HBV antigens in the context of an acute but limited infection could be harnessed for this purpose. This creates the need to better define if Tregs do also limit the response to acute infection and how this could be circumvented. We addressed these questions using the attenuated vaccinia virus MVA that is extensively being evaluated in clinical trials as a viral vector vaccine. Taking advantage of a mouse model that allows for specific depletion of Foxp3-positive Tregs we found that in the absence of Tregs, primary immune responses against recombinant MVA expressing the model antigen OVA were significantly increased (2-3 fold) and the phenotype of CD8 T cells shifted towards more differentiated effector cells (CD62Llow/CD127low). Interestingly, absolute numbers of central memory cells (CD62Lhigh/CD127high) were equal in the absence or presence of Tregs. Priming under Treg-depletion led to enhanced numbers of monofunctional T-cells (IFNγ+IL-2-TNFα-), while polyfunctional T cells (IFNγ+IL-2+TNFα+) considered as crucial for protective immunity were induced to the same level as in control animals. Unexpectedly, the higher number of T cells generated in the absence of Tregs was reflected in the early (d30), but not in the long-term memory phase (d70). There was no difference in the quality of induced T cells based on in vivo cytotoxicity assays or their ability to expand upon booster vaccination. Interestingly, the Treg effects appeared to be antigen specific and could be prevented by defined antigen formulations. Our data suggest that removal of Tregs can greatly amplify the number of fully differentiated T cells during the acute immune response but does not influence the long-term memory T cell pool. Therefore, interference with Treg function may not improve prophylactic vaccinations but might be of great importance for therapeutic settings.
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Publikationstyp Sonstiges: Vortrag
Konferenztitel International Meeting 2009
Konferzenzdatum 30th August - 02nd September 2009
Konferenzort Tour, France