Abstracts (complete list) - Wissenschaft Online

Bernd Lepenies, Klaus Pfeffer, Michelle Hurchla, Theresa Murphy, Kenneth Murphy,
Juliane Oetzel, Bernhard Fleischer, Thomas Jacobs
B and T lymphocyte attenuator (BTLA) ligation prevents
cerebral malaria during P. berghei ANKA infection
BTLA (CD272) is a coinhibitory receptor that is expressed on T and B cells and dampens
T cell activation. In this study, we analyzed the function of BTLA during infection with P.
berghei ANKA. This strain provokes a strong activation of T cells that is in C57BL/6 mice
associated with a pathology that resembles cerebral malaria in humans. During the
course of infection we found an induction of BTLA in several organs, which was either
due to up-regulation of BTLA expression on activated T cells in the spleen or due to
infiltration of BTLA-expressing T cells into several organs. In the brain we observed a
marked induction of BTLA and its ligand HVEM during cerebral malaria, which was
accompanied by an accumulation of predominantly CD8+ T cells, but also of CD4+ T
cells. Application of an anti-BTLA mAb caused a significantly reduced incidence of
cerebral malaria compared to control Ig. Treatment with this antibody also led to a
decreased number of T cells that sequestered into the brain of P. berghei ANKA-infected
mice. Our findings indicate that BTLA/HVEM interactions are functionally involved in
sequestration of T cells in brain capillaries and that BTLA engagement is of importance
to prevent immunopathology during infection with P. berghei ANKA. This study suggests
that BTLA is a potential target for therapeutic interventions in severe malaria and might
also have implications for the treatment of other inflammatory processes.