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DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigen

Citation

Bellette, BM and Woods, GM and Wozniak, TM and Doherty, KV and Muller, HK, DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigen, Immunology, 110, (4) pp. 466-473. ISSN 0019-2805 (2003) [Refereed Article]

DOI: doi:10.1111/j.1365-2567.2003.01759.x

Abstract

Antigen treatment of neonatal epidermis results in antigen-specific immune suppression. Compared with adult counterparts, neonatal Langerhans' cells (LC) demonstrate an impaired ability to transport antigen to the lymph node (LN). As it is possible that neonatal LC have a reduced ability to endocytose antigen, we evaluated the acquisition of endocytic function, the expression of uptake receptors and the internalization of soluble and small particulate antigens in neonatal, juvenile and adult mice. Although LC from 4-day-old mice were weakly positive for the mannose-type receptor, Langerin, they were capable of internalizing fluorescein isothiocyanate (FITC)-dextran, but to a lesser extent than LC from 6-week-old mice. However, when ratio data were calculated to account for variations in fluorescence intensity at 4°, it was demonstrated that neonatal LC continued to internalize antigen over a longer period of time than adult mice and, as the ratios were much higher, that neonatal cells were also relatively more efficient in antigen uptake. When receptors for mannan and mannose were competitively blocked, LC from neonatal mice, but not adult mice, could still efficiently internalize FITC-dextran, Consequently, the uptake of FITC-dextran, in part, occurred via alternative receptors or a receptor-independent fluid-phase pathway. A feasible pathway is macropinocytosis, as LC from 4-day-old mice demonstrated a reduction in FITC-dextran internalization by the macropinocytosis inhibitor, wortmannin. Evidence of a functional macropinocytosis pathway in neonatal LC was further supported by internalization of the soluble tracer Lucifer Yellow (LY). We conclude that neonatal LC preferentially utilize a wortmannin-sensitive, fluid-phase pathway, rather than receptor-mediated endocytosis, to internalize antigen. As neonatal LC are capable of sampling their environment without inducing immunity, this may serve to avoid inappropriate immune responses during the neonatal period.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Bellette, BM (Ms Bernadette Bellette)
Author:Woods, GM (Professor Gregory Woods)
Author:Wozniak, TM (Miss Teresa Wozniak)
Author:Doherty, KV (Dr Kathleen Doherty)
Author:Muller, HK (Professor Konrad Muller)
ID Code:28191
Year Published:2003
Web of Science® Times Cited:14
Deposited By:Pathology
Deposited On:2003-08-01
Last Modified:2015-08-17
Downloads:0

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