gamma delta-T cells expressing NK receptors predominate over NK cells and conventional T cells in the innate IFN-gamma response to Plasmodium falciparum malaria

D&#39;Ombrain, MC; Hansen, DS; Simpson, KM; Schofield, L

Author(s): D'Ombrain, MC; Hansen, DS; Simpson, KM; Schofield, L;
Details: Publication Year 2007-07,Volume 37,Issue #7,Page 1864-1873
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Rapid production of interferon-gamma (IFN-gamma) in response to malaria by the innate immune system may determine resistance to infection, or inflammatory disease. However, conflicting reports exist regarding the identity of IFN-gamma-producing cells that rapidly respond to Plasmodium falciparum. To clarify this area, we undertook detailed phenotyping of IFN-gamma-producing cells across a panel of naive human donors following 24-h exposure to live schizont-infected red blood cells (iRBC). Here, we show that NK cells comprise only a small proportion of IFN-gamma-responding cells and that IFN-gamma production is unaffected by NK cell depletion. Instead, gamma delta-T cells represent the predominant source of innate IFN-gamma, with the majority of responding gamma delta-T cells expressing NK receptors. Malaria-responsive gamma delta-T cells more frequently expressed NKG2A compared to non-responding gamma delta-T cells, while non-responding gamma delta-T cells more frequently expressed CD158a/KIR2DL1. Unlike long-term gamma delta-T cell responses to iRBC, alpha beta-T cell help was not required for innate gamma delta-T cell responses. Diversity was observed among donors in total IFN-gamma output. This was positively associated with CD94 expression on IFN-gamma(+) NK-like gamma delta-T cells. Applied to longitudinal cohort studies in endemic regions, similar comparative phenotyping should allow assessment of the contribution of diverse cell populations and regulatory receptors to risk of infection and disease.
Publisher: WILEY-V C H VERLAG GMBH
Keywords: MURINE CEREBRAL MALARIA; NATURAL-KILLER COMPLEX; INFECTED ERYTHROCYTES; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; HLA-E; PATHOGENESIS; ANTIGENS; LYMPHOCYTES; INTERFERON
Publisher's Version: https://doi.org/10.1002/eji.200636889
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-07-01 12:00:00