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Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy.
Miller MJ, Wei SH, Cahalan MD, Parker I
Proc Natl Acad Sci U S A 2003 Mar 4 100(5):2604-9 [abstract on PubMed] [related articles] [order article]
Selected by | Michael Dustin / Ulrich Von Andrian
First evaluation 26 Mar 2003 | Latest evaluation 12 Aug 2003
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Faculty Comments
Faculty Member Comments
Michael Dustin
New York University School of Medicine, United States
IMMUNOLOGY

New Finding
This paper reports that T lymphocytes in lymph nodes in vivo display a spectacular motility that can be described as a random walk within the T cell zones. This behavior suggests that lymphocytes encounter antigen-presenting cells through autonomous motility without a need for specific chemoattraction. This study and previous organ culture studies from the same lab have provoked a paradigm shift in thinking about the early moments of the T cell-dendritic cell interaction. T lymphocytes from DO.11 T cell receptor transgenic mice were labeled with carboxyfluorescein succinimidylester (CFSE) and were transferred into 4 week old MHC identical normal recipient mice. The mice were anesthetized and the inguinal lymph node was surgically exposed and mounted in a temperature controlled stage and the interior of the lymph node was imaged with a two-photon laser scanning microscope through natural windows in the adipose tissue surrounding the lymph node in mice of this age. Blood flow was maintained as demonstrated by the visualization of labeled T cells flowing in the microcirculation of the node. Lymph flow was not verified, but the avoidance of surgery near the node to remove adipose tissue means that afferent and efferent lymphatic were likely intact. Z-stacks were obtained of lymph nodes with sufficient time resolution to track the migration of T cells within the T cell zones. The average velocity was 10.2-11.5 micrometers/min with a peak velocity of up to 25 micrometers/min. While cells sometimes briefly paused, there appeared to be no population of immobile cells. The direction of motion appeared to be random in both parallel to the capsule and axially. While the T cell frequently moved in a straight line for ~30 micrometers before changing direction, the movement at longer time scales was well modeled by a random walk where the slot of displacement vs the square root of time was linear. The animals were maintained during anesthesia with 95% oxygen and 5% carbon dioxide, a gas mix that is used to elevate tissue oxygen levels. Therefore the relationship of tissue O2 levels in this system to those in a normal awake mouse is not known. The high rate of T cell autonomous motility described here also provides a clear model for immune surveillance in lymph nodes in which T cells may encounter many potential antigen presenting cells in search of the "antigenic needle in a haystack" to quote the authors.

Evaluated 12 Aug 2003
Ulrich Von Andrian
Harvard Medical School, United States
IMMUNOLOGY

Confirmation
Tech Advance
This in vivo analysis of the migratory dynamics of T cells in inguinal lymph nodes validates earlier in vitro observations by this group in excised lymph nodes, which have shown that naive T cells migrate very rapidly and with apparently random directionality. The finding that T cells act as autonomous agents challenges the concept that interstitial chemokine gradients channel streams of migrating T cells within lymph nodes.

Evaluated 26 Mar 2003
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 2003 Mar 4 100 (5) :2604-9 http://www.facultyof1000.com/article/12601158/evaluation

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

Michael Dustin: Faculty of 1000 Biology, 12 Aug 2003 http://www.facultyof1000.com/article/12601158/evaluation

Ulrich Von Andrian: Faculty of 1000 Biology, 26 Mar 2003 http://www.facultyof1000.com/article/12601158/evaluation


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