Cell-autonomous and environmental contributions to the interstitial migration of T cells

A key to understanding the functioning of the immune system is to define the mechanisms that facilitate directed lymphocyte migration to and within tissues. The recent development of improved imaging technologies, most prominently multi-photon microscopy, has enabled the dynamic visualization of immune cells in real-time directly within intact tissues. Intravital imaging approaches have revealed high spontaneous migratory activity of T cells in secondary lymphoid organs and inflamed tissues. Experimental evidence points towards both environmental and cell-intrinsic cues involved in the regulation of lymphocyte motility in the interstitial space. Based on these data, several conceptually distinct models have been proposed in order to explain the coordination of lymphocyte migration both at the single cell and population level. These range from “stochastic” models, where chance is the major driving force, to “deterministic” models, where the architecture of the microenvironment dictates the migratory trajectory of cells. In this review, we focus on recent advances in understanding naïve and effector T cell migration in vivo. In addition, we discuss some of the contradictory experimental findings in the context of theoretical models of migrating leukocytes

Feasibility of Bone Perfusion Evaluation in Cadavers Using Indocyanine Green Fluorescence Angiography

Summary:. Bone perfusion evaluation methods in cadaver studies have yet to be established. The aim of this report was to introduce and validate the feasibility of indocyanine green (ICG) fluorescence angiography for evaluation of bone perfusion in the femoral medial condyle in cadavers. In 4 fresh nonembalmed cadavers (2 female), the descending genicular artery was dissected and carefully cannulated bilaterally. A 10 mL solution containing 5 mL ICG solution and 5 mL methylene blue solution was injected into the descending genicular artery. After the injection, the medial femoral condyle was cut with an oscillating saw. A photograph was taken of the cut ends of the bone. The cut ends of the bones were observed using a near-infrared camera. Images corresponding to the previously taken photographs of the cut ends were captured for comparative analysis. After injection of methylene blue and ICG, the blue dye could be seen in the periosteum in all specimens, but not inside the cortex or the cancellous region of the bone. When observed with ICG fluorescence angiography, however, the cancellous region was highlighted through small perforators penetrating the periosteum. Perfusion inside the medial femoral condyle in cadavers was confirmed using ICG fluorescence angiography. Our method can be especially beneficial in confirming the bone perfusion of a new bone flap based on a particular artery, both in cadavers as well as in patients, because ICG can be injected into specific arteries

Visualization of Skin Perfusion by Indocyanine Green Fluorescence Angiography—A Feasibility Study

Summary:. Plastic and reconstructive surgery relies on the knowledge of angiosomes in the raising of microsurgical flaps. Growing interest in muscle-sparing perforator flaps calls for reliable methods to assess the clinical feasibility of new donor sites in anatomical studies. Several injection techniques are known for the evaluation of vascular territories. Indocyanine green–based fluorescence angiography has found wide application in the clinical assessment of tissue perfusion. In this article, the use of indocyanine green–based fluorescence angiography for the assessment of perforasomes in anatomical studies is described for the first time

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Chemokines play a central role in regulating processes essential to the immune function of T cells(1-3), such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8(+) T cells to control the pathogen T. gondii in the brains of chronically infected mice. This chemokine boosts T cell function in two different ways: it maintains the effector T cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Remarkably, these statistics are not Brownian; rather, CD8(+) T cell motility in the brain is well described by a generalized Lévy walk. According to our model, this surprising feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8(+) T cell behavior is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys(4-10), and CXCL10 aids T cells in shortening the average time to find rare targets

Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells

Type 2 immunity is critical for defense against cutaneous infections but also underlies the development of allergic skin diseases. We report the identification in normal mouse dermis of an abundant, phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. Treatment of mice deficient in recombination-activating gene 1 (Rag1−/−) with IL-2 resulted in the population expansion of activated, IL-5-producing dermal ILC2 cells, which led to spontaneous dermatitis characterized by eosinophil infiltrates and activated mast cells. Our data show that ILC2 cells have both pro- and anti-inflammatory properties and identify a previously unknown interactive pathway between two innate populations of cells of the immune system linked to type 2 immunity and allergic diseases.Ben Roediger, Ryan Kyle, Kwok Ho Yip, Nital Sumaria, Thomas V Guy, Brian S Kim, Andrew J Mitchell, Szun S Tay, Rohit Jain, Elizabeth Forbes-Blom, Xi Chen, Philip L Tong, Holly A Bolton, David Artis, William E Paul, Barbara Fazekas de St Groth, Michele A Grimbaldeston, Graham Le Gros, & Wolfgang Weninge