Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum.
The immunodominant CD4 T cell epitope region, Th2R, of the circumsporozoite protein of Plasmodium falciparum is highly polymorphic. Such variation might be utilized by the parasite to escape from or interfere with CD4 T cell effector functions. Here, we show that costimulation with naturally occurring altered peptide ligands (APL) can induce a rapid change from IFNgamma production to the immunosuppressive mediator interleukin 10 (IL-10). This mechanism may contribute to the low levels of T cell responses observed to this pathogen in malaria-endemic areas.
Plebanski
M
M
Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. mplebans@ari.unimelb.edu.au
Flanagan
K L
KL
Lee
E A
EA
Reece
W H
WH
Hart
K
K
Gelder
C
C
Gillespie
G
G
Pinder
M
M
Hill
A V
AV
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D016056:Immunodominant Epitopes / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology; D016415:Sequence Alignment
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D016753:Interleukin-10; D007371:Interferon-gamma