NDLI: The absence of lymphoid CD8+ dendritic cell maturation in L-selectin-/- respiratory compartment attenuates antiviral immunity.

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The absence of lymphoid CD8+ dendritic cell maturation in L-selectin-/- respiratory compartment attenuates antiviral immunity.

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The absence of lymphoid CD8+ dendritic cell maturation in L-selectin-/- respiratory compartment attenuates antiviral immunity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Callis, Gayle Kochetkova, Irina Wang, Xinhai Riccardi, Carol Pascual, David W.
Description	Country affiliation: United States Author Affiliation: Pascual DW ( Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA. dpascual@montana.edu)
Abstract	Intratracheal instillation of L-selectin-deficient (L-Sel(-/-)) mice with an adenovirus 2 (Ad2) vector resulted in the lack of respiratory Ad2- or beta-galactosidase-specific CTLs with concomitant long-lived beta-galactosidase transgene expression in the lungs. The absence of Ag-specific CTLs was attributed to a deficiency in lymphoid CD11c(+)CD8(+) dendritic cells (DCs) in the lower respiratory lymph nodes (LRLNs). To enable L-Sel(-/-) CTL activity, cell-sorted L-Sel(-/-)CD8(+) T cells were cocultured with cell-sorted L-Sel(+/+)CD8(+) or CD8(-) DCs or L-Sel(-/-)CD8(-) DCs. Only the CD8(+) DCs restored CTL activity; L-Sel(-/-)CD8(-) DCs failed to support L-Sel(+/+) CTLs because these remained immature, lacking the ability to express costimulatory molecules CD40, CD80, or CD86. Although no lung CD8(+) DCs were detected, the DC environment remained suppressive in L-Sel(-/-) mice evident by the lack of CTL responses following adenoviral challenge with OVA in recipient L-Sel(-/-) adoptively transferred with OT-1 CD8(+) T cells. To assess whether the L-Sel(-/-)CD8(-) DCs could be induced into maturity, microbial stimulation studies were performed showing the failure of L-Sel(-/-) LRLN to make matured DCs. When L-Sel(-/-) mice were subjected in vivo to microbial activation before Ad2 vector dosing, CTL activity was restored stimulating the renewed presence of LRLN CD8(+) DCs in L-Sel(-/-) mice. These studies show that impairment of L-Sel(-/-) DC maturation results in insufficient mature DCs that require microbial activation to restore increases in respiratory CD8(+) DCs to support CTL responses.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	2
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenoviridae Immunology Antigens, Cd8 Dendritic Cells L-selectin Lung Lymph Nodes T-lymphocytes, Cytotoxic Genetics Animals Antigens, Cd40 Metabolism Antigens, Cd80 Antigens, Cd86 Cell Line, Tumor Genetic Vectors Lipopolysaccharides Lymphocyte Subsets Mice Mice, Inbred C57bl Mice, Knockout Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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