Ligation of B and T lymphocyte attenuator prevents the genesis of experimental cerebral malaria

Bernd Lepenies, Klaus Pfeffer, Michelle A. Hurchla, Theresa L. Murphy, Kenneth M. Murphy, Juliane Oetzel, Bernhard Fleischer, Thomas Jacobs

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

B and T lymphocyte attenuator (BTLA; CD272) is a coinhibitory receptor that is predominantly expressed on T and B cells and dampens T cell activation. In this study, we analyzed the function of BTLA during infection with Plasmodium berghei ANKA. Infection of C57BL/6 mice with this strain leads to sequestration of leukocytes in brain capillaries that is associated with a pathology resembling 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 T cells in the spleen or due to infiltration of BTLA-expressing T cells into the brain. In the brain, we observed a marked induction of BTLA and its ligand herpesvirus entry mediator during cerebral malaria, which was accompanied by an accumulation of predominantly CD8 + T cells, but also CD4+ T cells. Application of an agonistic anti-BTLA mAb caused a significantly reduced incidence of cerebral malaria compared with control mice. Treatment with this Ab also led to a decreased number of T cells that were sequestered in the brain of P. berghei ANKA-infected mice. Our findings indicate that BTLA-herpesvirus entry mediator interactions are functionally involved in T cell regulation during P. berghei ANKA infection of mice and that BTLA is a potential target for therapeutic interventions in severe malaria.

Original languageEnglish
Pages (from-to)4093-4100
Number of pages8
JournalJournal of Immunology
Volume179
Issue number6
DOIs
StatePublished - Sep 15 2007

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