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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.

Original publication

DOI

10.1016/j.immuni.2005.08.006

Type

Journal article

Journal

Immunity

Publication Date

09/2005

Volume

23

Pages

287 - 296

Keywords

Animals, CD4 Antigens, Clinical Trials as Topic, DNA-Binding Proteins, Forkhead Transcription Factors, Humans, Malaria, Falciparum, Plasmodium falciparum, Receptors, Interleukin-2, T-Lymphocytes, Transforming Growth Factor beta, Up-Regulation