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Reduced CD3/TCR complex expression leads to immunosuppression during Plasmodium falciparum malaria.

Abstract
Inhibition of T cell function is an important pathological feature in malaria. We investigated which T cell population is reduced contributing to immunosuppression. We examined protein and RNA level of various cell receptors, specific for T cells in children having Plasmodium falciparum infection and compared those to healthy children of the same age. We observe reduced levels of cluster of differentiation (CD)3 and T cell receptor (TCR)alphabeta in both RNA and protein expression level. This reduced expression was associated with a collapsed membrane asymmetry as determined by enhanced annexinV binding. Also human leukocyte antigen (HLA)-A,B,C- and HLA-DR-positive cells increasingly bound annexinV. The enhanced binding of annexinV was paralleled by a reduced expression of transcription factors such as T cell transcription factor 7 and GATA binding protein 3, which are involved in the expression of T cell specific genes. Also the expression of the transcription factors major histocompatibility complex class II transactivator and regulatory factor X 5, which are part of the HLA transcription machinery, is reduced during infection. We show that two mechanisms may lead to a suppression of the immune system during malaria: cell damage and reduction of gene expression of the CD3/TCR complex.
AuthorsYvonne Kalmbach, Angelica B W Boldt, Benjamin Mordmüller, Maryvonne Kombila, Martin P Grobusch, Peter G Kremsner, Jürgen F J Kun
JournalParasitology research (Parasitol Res) Vol. 104 Issue 3 Pg. 575-82 (Feb 2009) ISSN: 0932-0113 [Print] Germany
PMID18975003 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Annexin A5
  • CD3 Complex
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors
Topics
  • Animals
  • Annexin A5 (metabolism)
  • CD3 Complex (biosynthesis)
  • Cell Membrane (metabolism)
  • Child
  • Child, Preschool
  • Humans
  • Immunosuppression Therapy
  • Infant
  • Malaria, Falciparum (immunology)
  • Plasmodium falciparum (immunology)
  • Receptors, Antigen, T-Cell, alpha-beta (biosynthesis)
  • Transcription Factors (biosynthesis)

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