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Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells

Intercellular adhesion molecule-3 is the predominant co-stimulatory ligand for leukocyte function antigen-1 on human blood dendritic cells

Authors :
Alexander D. McLellan
William Egner
Gary C. Starling
Jonathan Fawcett
David Simmons
R. V. Sorg
Derek N.J. Hart
Source :
European Journal of Immunology. 25:2528-2532
Publication Year :
1995
Publisher :
Wiley, 1995.

Abstract

Haematology/Immunology Research Group, Christchurch Hospital and Christchurch School of Medicine, Christchurch, New Zealand ICRF Laboratories, Institute of Molecular Medicine, Oxford, GB Dendritic cells (DC) are potent stimulators of primary T lymphocyte responses to foreign antigen. The initial DC-T lymphocyte interaction involves the binding of the adhesion molecule leukocyte function antigen-1 (LFA-1; CDlldCD18) on the T lymphocyte to an intercellular adhesion molecule (ICAM) on DC. Although blood and tonsil DC express ICAM-1 (CD54) and ICAM-2 (CD102) on their surface, anti-ICAM-1 and anti-ICAM-2 monoclonal antibodies (mAb) have little inhibitory activity on the DC-stimulated mixed leukocyte reaction (MLR). We therefore examined the expression of the more recently identified LFA-1 ligand, ICAM-3 (CD50), in comparison to ICAM-1 and ICAM-2 on blood DC and sought a functional role for ICAM-3 in DC-mediated T lympho- cyte responses. Resting blood DC expressed significantly more ICAM-3 than ICAM-1 or ICAM-2 as assessed by flow cytometry. Treatment of resting DC with interferon-y led to increased expression of ICAM-1; however, ICAM-2 and ICAM-3 levels remained relatively constant. Solid-phase recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co-stimulate CD4' T lymphocyte proliferation in conjunction with suboptimal solid-phase CD3 mAb 64.1. However, the anti-ICAM-3 mAb CAL 3.10 inhibited a DC- stimulated MLR to a greater extent than anti-ICAM-1 or anti-ICAM-2 reagents and appeared to act by blocking the DC ICAM-3- T lymphocyte LFA-1 interac- tion. As ICAM-3 is the predominant LFA-1 ligand on resting blood DC, we pos- tulate that DC may utilize ICAM-3 for initial DC- T lymphocyte interactions, and that ICAM-1, which is up-regulated upon DC activation, and/or ICAM-2, may contribute to DC migration or later phases of the T lymphocyte activation process.

Details

ISSN :
15214141 and 00142980
Volume :
25
Database :
OpenAIRE
Journal :
European Journal of Immunology
Accession number :
edsair.doi.dedup.....08cec2cac66c38bacf193e2d0fa8877c
Full Text :
https://doi.org/10.1002/eji.1830250918