Research Group Heussler (Malaria I) - Bernhard-Nocht-Institut für ...

low level chronic replication of the SIV∆nef, expands
the numbers of γδ T cells at the portal of entry.
One of the most important immunoarchitectural
changes was that the number of mature DCs in the
tonsils strikingly expanded in the vaccinated animals
but not in the unvaccinated controls, as assessed by
staining for the DC-LAMP and the CD83 markers. In
naïve challenged controls, and in vaccinated animals
prior to challenge, the frequency of mature DCs was
similar to normal tonsillar tissue. However, in the vaccinated
challenged animals, the frequency of mature DCs
increased almost 2 fold at day 4. Then DC numbers
began to fall at day 7/8 and were back to baseline at
day 14/15. In the naïve controls, there was no change
in DC numbers at day 4/7, but these began to fall below
normal at a later time point. Therefore one of the
distinctive features of the portal of entry of vaccinated
challenged animals is an acute expansion of mature
DCs, whereas in unvaccinated monkeys, DC numbers
actually drop considerably during acute infection (3).
In conclusion, SIV∆NU vaccination can selectively block
early infection at the entry site of an immunodeficiency
virus, which we propose depends at least in part upon
innate protective functions by dendritic and γδ T cells.
γδ Tcells can produce chemokines and cytokines that
promote DC maturation (Leslie D.S. et al. J. Exp. Med.
2002; 196:1575). Mature DC could shift the host toward
adoptive immune responses that impede replication
of the highly pathogenic wild-type virus during primary
infection.
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Selected Publications
• Stahl-Hennig C et al. (1999). Science 285: 1261-1265
• Stahl-Hennig, C et al. (2002). J. Virol. 76: 688-696
• Tenner-Racz K et al. (2004). Proc. Natl. Acad. Sci.
USA 101: 3017-3022
Funding
• European Community Contract QLK2-CT-1999-01215
Cooperating Partners
• Ralph M. Steinman, Rockefeller University,
New York, USA
• Christiane Stahl-Hennig, German Primate Centre,
Göttingen (DPZ)
• Klaus Überla, Ruhr-University Bochum
• Manfred Dierich /Heribert Stoiber, Institute of Hygiene
and Social Medicine, Innsbruck, Austria
• Ralf Ignatius, Charité - University Medicine Berlin
• Gudmundur Gerogsson, University of Iceland,
Reykjavik, Iceland
• Gianni Pozzi, University of Siena, Italy
• Carlo Baroni, University „La Sapienza”, Roma, Italy
• Marco Baggiolini, Mariagrazia Uguccioni, Institute for
Research in Biomedicine, Bellinzona, Switzerland
• Jonathan Heeney, Biomedical Primate Research
Center, Rijswijk, Netherlands
Investigators
• Paul Racz
• Klara Tenner-Racz
Tropical Medicine Section
Figure 1: Early protection against SIV challenge. Wild type SIVmac251 was detected by in situ hybridization (black) and immunolabeling
for nef protein (gray cytoplasmic staining) in the unvaccinated controls but not in SIV∆NU vaccinees.