Elsevier

Seminars in Immunology

Volume 17, Issue 6, December 2005, Pages 421-430
Seminars in Immunology

Review
Tracking thymocyte migration in situ

https://doi.org/10.1016/j.smim.2005.09.005Get rights and content

Abstract

The dynamic process of thymocyte migration can now be visualized in real-time and in the context of the native thymic environment. With improved computational resources, key information can be extracted from real-time imaging data and the migratory behaviors of developing thymocytes can be quantitated. The extraction and exploitation of three dimensional data through time is providing new insight into the nature and regulation of intrathymic migration. In this review we discuss this interdisciplinary approach and the promise it holds for the study of thymocyte migration in situ.

Introduction

The travels of a developing thymocyte are a curious business. According to our current understanding, precursors to the T cell lineage enter at an interior site of the thymus, the cortico-medullary junction (CMJ) (Fig. 1) [1]. After a stay in this general vicinity, developing thymocytes migrate outwards across the cortex to the thymic capsule [2], only to reverse their migratory direction and return back inward to the interior region of the medulla before departure to their final destination, the periphery [3], [4]. Each of these legs of the journey is associated in time and space with important developmental milestones for the maturing thymocyte [4], [5], [6], [7], [8]. The reasons behind this migratory pattern are not obvious, and the regulation of thymocyte trafficking is far from understood. New tools afforded by advanced imaging techniques in combination with computer-assisted cell tracking offer great promise in elucidating the mechanisms by which cells move through their native environment.

Section snippets

Thymocyte migration: from short range propulsion to long range navigation

The distances that a thymocyte must traverse during its 3–4 weeks of development in the thymus represents a marathon on the length scale of the cell. In order to accomplish its journey, the mechanics of cell propulsion must be coupled to navigational mechanisms to effect the long range movement of thymocytes across the thymic cortex. Impairment of either short range propulsion or of long range guidance mechanisms can lead to migratory defects and inefficient T cell production [9], [10], [11],

Chemokine action in trafficking regulation

Collectively, the above studies have begun to reveal the critical factors that underlie the dynamic process of thymocyte migration. Naturally, as is always the case in science, these new findings have led to more questions, in particular is the question of how chemokines operate in the process of thymocyte migration. Because chemokines are best known for their role in inducing chemotaxis, the directed migration in the direction of a stimulus, it is often assumed that they impart their effects

Two photon imaging to visualize intrathymic migration

Cell migration is a process that is inherently a state of motion. Consequently, there are some questions pertaining to mechanism that cannot be answered from inspection of cell positioning at a single time point, but rather requires the visualization of cells as they move. For example, the question of whether a given chemokine increases random cell motility or provides directional guidance to cell movement can only be discerned by visualizing and quantitating the real-time motility properties

Positive selection and its impact on thymocyte migration

In situ analysis of fixed thymic sections has shown tight compartmentalization of developmental intermediates within the thymus. CD4+CD8+ double-positive thymocytes are localized to the outer thymic region of the cortex, whereas CD4+CD8− and CD8+CD4− single-positive thymocytes are restricted to the inner thymic region of the medulla. Based on our knowledge that the SP developmental stage follows the DP stage in time, we have inferred that there must be a migratory event that occurs in concert

Advanced imaging and the computational sciences: promises and challenges

TPLSM is proving to be an invaluable tool for the study of lymphocyte behavior in situ. Currently, however, multi-photon imaging technology faces two primary challenges. First is the need to achieve greater depths of imaging, which would allow the visualization of more remote anatomical compartments. Meeting this challenge will require the use of even longer excitation wavelengths, which enables deeper penetration into living tissues. Unfortunately, with current technology, there is a

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