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T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node.
Miller MJ, Hejazi AS, Wei SH, Cahalan MD, Parker I
Proc Natl Acad Sci U S A 2004 Jan 27 101(4):998-1003 [abstract on PubMed] [related articles] [order article]
Selected by | Andrea Sant / Rick Tarleton / Michael Dustin
First evaluation 3 Feb 2004 | Latest evaluation 10 Aug 2004
Relevant Sections

Faculty Comments
Faculty Member Comments
Andrea Sant
University of Rochester Medical Center, United States
IMMUNOLOGY

New Finding
Tech Advance
This paper deals with the important issue of the mechanisms through which rare naive T cells encounter low numbers of recently emigrated antigen-bearing dendritic cells in peripheral lymph nodes. The authors employ a novel approach to activate and label peripheral dendritic cells and to follow their migration and encounter with T cells in the draining lymph nodes using two photon microscopy. Their results show that extended and rapidly moving dendrites from the dendritic cell body allow a typical dendritic cell to collectively scan up to 5000 T cells per hour. This sweeping scanning pattern of dendritic cells, coupled with rapid and random motility of T cells accounts for the ultimate contact between antigen bearing dendritic cells with rare antigen specific T cells and thus the initiation of an antigen specific T cell response.

Evaluated 10 Aug 2004
Rick Tarleton
University of Georgia, United States
IMMUNOLOGY

Confirmation
New Finding
Using two-photon microscopy and injection of CFSE (carboxyfluorescein succinimidyl ester) in alum, this study shows that in vivo labelled dendritic cells (DCs) traffic from the skin to the draining lymph node where the sweeping action of their dendrites and the random movement of T cells allow each DC to make an estimated 5000 T cell contacts per hour. At this rate, as few as 100 antigen-bearing DC were determined to be able to efficiently screen for low frequency antigen-specific T cells (1 in 10e6) in as little as 6 hours.

Evaluated 24 Feb 2004
Michael Dustin
New York University School of Medicine, United States
IMMUNOLOGY

Confirmation
Tech Advance
This paper develops a new and highly effective method for labeling dendritic cells in tissues for later visualization in explanted lymph nodes or detection by flow cytometry. They find that the T cell scanning rate of dendritic cells is 10-fold higher than earlier estimates, probably due to better resolution of fine, dendritic processes which make up much of dendritic cell surface area available for T cell contact. The method consists of mixing microgram amounts of carboxyfluorescein succinimidyl ester (CFSE) with alum and injecting it subcutaneously. The CFSE appears to be trapped in the alum depot such that it does not directly drain to the lymph node, but does label dermal dendritic cells that migrate and reach the lymph node after several hours. Fluorescent protein antigens could also be included in the alum suspension and could be detected associated with the CFSE labeled dendritic cells. This method is analogous to the FITC painting method for labeling Langerhan's cells. An advantage of this approach is that it allows visualization of cell populations that are directly relevant to vaccination strategies. The authors provide additional support for their earlier proposal that T cell repertoire scanning is primarily accomplished by rapid, autonomous migration of T cells through a field of slower migrating dendritic cells elaborating a high surface area to form ~300 contacts at any time and 5000 contacts per hour per dendritic cell.

Evaluated 3 Feb 2004
Faculty Comments

How to cite the Faculty of 1000 Biology evaluation(s) for this paper

1) To cite all the evaluations for this article:

Faculty of 1000 Biology: evaluations for Miller MJ et al Proc Natl Acad Sci U S A 2004 Jan 27 101 (4) :998-1003 http://www.facultyof1000.com/article/14722354/evaluation

2) To cite an evaluation by a specific Faculty member:

Andrea Sant: Faculty of 1000 Biology, 10 Aug 2004 http://www.facultyof1000.com/article/14722354/evaluation

Rick Tarleton: Faculty of 1000 Biology, 24 Feb 2004 http://www.facultyof1000.com/article/14722354/evaluation

Michael Dustin: Faculty of 1000 Biology, 3 Feb 2004 http://www.facultyof1000.com/article/14722354/evaluation


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