Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection.
Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.
Walther
Michael
M
Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Churchill Hospital, Oxford OX3 7LJ, United Kingdom.
Tongren
Jon Eric
JE
Andrews
Laura
L
Korbel
Daniel
D
King
Elizabeth
E
Fletcher
Helen
H
Andersen
Rikke F
RF
Bejon
Philip
P
Thompson
Fiona
F
Dunachie
Susanna J
SJ
Edele
Fanny
F
de Souza
J Brian
JB
Sinden
Robert E
RE
Gilbert
Sarah C
SC
Riley
Eleanor M
EM
Hill
Adrian V S
AV
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*; D015854:Up-Regulation
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta