Acute in vivo exposure to interferon-gamma enables resident brain dendritic cells to become effective antigen presenting cells.
Dendritic cells (DC) are the professional antigen presenting cells (APC) that bridge the innate and adaptive immune system. Previously, in a CD11c/EYFP transgenic mouse developed to study DC functions, we anatomically mapped and phenotypically characterized a discrete population of EYFP(+) cells within the microglia that we termed brain dendritic cells (bDC). In this study, we advanced our knowledge of the function of these cells in the CD11c/EYFP transgenic mouse and its chimeras, using acute stimuli of stereotaxically inoculated IFNgamma or IL-4 into the CNS. The administration of IFNgamma increased the number of EYFP(+)bDC but did not recruit peripheral DC into the CNS. IFNgamma, but not IL-4, upregulated the expression levels of major histocompatibility class II (MHC-II). In addition, IFNgamma-activated EYFP(+)bDC induced antigen-specific naïve CD4 T cells to proliferate and secrete Th1/Th17 cytokines. Activated bDC were also able to stimulate naïve CD8 T cells. Collectively, these data reveal the Th1 cytokine IFNgamma, but not the Th2 cytokine IL4, induces bDC to up-regulate MHC-II and become competent APC.
Gottfried-Blackmore
Andres
A
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA.
Kaunzner
Ulrike W
UW
Idoyaga
Juliana
J
Felger
Jennifer C
JC
McEwen
Bruce S
BS
Bulloch
Karen
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000939:Epitopes / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance / Q000187:drug effects; D054400:Receptors, CCR7 / Q000378:metabolism
D001426:Bacterial Proteins; D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D008164:Luminescent Proteins; D054400:Receptors, CCR7; C054562:yellow fluorescent protein, Bacteria; D015847:Interleukin-4; D007371:Interferon-gamma