Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo.
Va14Ja18 natural T (iNKT) cells are innate, immunoregulatory lymphocytes that recognize CD1d-restricted lipid Ags such as alpha-galactosylceramide (alpha GalCer). The immunoregulatory functions of iNKT cells are dependent upon either IFN-gamma or IL-4 production by these cells. We hypothesized that alpha GalCer presentation by different CD1d-positive cell types elicits distinct iNKT cell functions. In this study we report that dendritic cells (DC) play a critical role in alpha GalCer-mediated activation of iNKT cells and subsequent transactivation of NK cells. Remarkably, B lymphocytes suppress DC-mediated iNKT and NK cell activation. Nevertheless, alpha GalCer presentation by B cells elicits low IL-4 responses from iNKT cells. This finding is particularly interesting because we demonstrate that NOD DC are defective in eliciting iNKT cell function, but their B cells preferentially activate this T cell subset to secrete low levels of IL-4. Thus, the differential immune outcome based on the type of APC that displays glycolipid Ags in vivo has implications for the design of therapies that harness the immunoregulatory functions of iNKT cells.
Bezbradica
Jelena S
JS
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Stanic
Aleksandar K
AK
Matsuki
Naoto
N
Bour-Jordan
Helene
H
Bluestone
Jeffrey A
JA
Thomas
James W
JW
Unutmaz
Derya
D
Van Kaer
Luc
L
Joyce
Sebastian
S
D000818:Animals; D000941:Antigens; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D003713:Dendritic Cells / Q000276:immunology*; D005699:Galactosylceramides / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000941:Antigens; D005699:Galactosylceramides; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma