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Lymphocyte Adhesion and Trafficking

Sirpa Jalkanen, Marko Salmi

EARLY LYMPHOCYTE PRECURSOR TRAFFICKING KEY CONCEPTS
TO THE PRIMARY LYMPHOID ORGANS Lymphocyte Recirculation

Lymphocyte trafficking begins at an early stage of human ontogeny • Lymphocytes recirculate continuously between blood and lymphoid
when lymphocyte precursor cells first appear and migrate into organs.
1-3
the primary lymphoid organs. The multipotent hematopoietic • 80% of lymphocytes enter the lymph nodes via specialized vessels
progenitor and stem cells from the yolk sac and from the called high endothelial venules (HEVs).
aorta–gonad–mesonephros migrate via the circulation to the • The remaining lymphocytes enter the lymph nodes together with
dendritic cells (DCs) and antigens via afferent lymphatics.
liver and the spleen, which are important organs that support • Lymphocytes leave the lymph nodes via efferent lymphatics.
lymphocyte production in the embryo (Chapters 2, 7), and then • Lymphocyte recirculation allows the lymphocytes to meet their cognate
into bone marrow. Thereafter, the developmental maturation of antigens and other leukocyte subsets to evoke an efficient immune
B cells takes place solely in bone marrow. T cells, in contrast, response.
require an additional migratory event, which involves the entry
of marrow-derived T-cell progenitors into the thymus (Chapter
4
8). These early T-cell progenitors enter the thymus via the vessels
in the cortical region. Concomitant with their differentiation Antigens gather into these secondary lymphoid organs by a
and maturation via positive and negative selection, they pass different route. Most antigens in the periphery can be taken up
from the cortex into the medulla. by dendritic cells (DCs) (Chapter 6), which subsequently migrate
2
into the secondary lymphoid organs via the afferent lymphatics.
These afferent lymph channels open into the subcapsular sinus
MIGRATION OF NAIVE MATURE LYMPHOCYTES of the lymph node. Individual DCs subsequently penetrate the
FROM BLOOD TO THE SECONDARY lymphatic endothelium and migrate into the stroma. Unbound,
LYMPHOID ORGANS or free, antigens that are being carried via the afferent lymphatics
through the body can diffuse into these secondary lymphoid
After completing their initial course of development, newly arisen organs, and then they can be captured by the professional
naïve B and T cells exit the primary lymphoid organs, travel antigen-presenting cells (APCs) of the lymph nodes. Lymph
through blood, and extravasate selectively to the secondary nodes thus serve as traps for the immune system, collecting
lymphoid organs. 2,5,6 These include peripheral lymph nodes, lymphocytes from blood and antigens from lymph (Fig. 11.2).
organized lymphoid tissues of the gut (e.g., Peyer patches and In these organs, lymphocytes percolate through the tissue in
2,7
the appendix), and the spleen (Chapter 2). In lymph nodes, most search of their cognate antigens. If a given lymphocyte does
lymphocyte trafficking from blood to tissues takes place in not find its antigen, it will leave the organ by entering the efferent
specialized postcapillary venules. The endothelial cells of the lymphatics that drain the medullary sinuses and is then trans-
venule exhibit a characteristic high cuboidal morphology that ported via a major lymphatic trunk, such as the thoracic duct,
has given them their name: high endothelial venules (HEVs). back into the large systemic veins. After reentering the circulation,
The protrusion of the surface of these endothelial cells into the the cell can randomly gain access to another lymph node, where
vascular lumen promotes the interaction of leukocytes in the it has another chance to extravasate into tissue and find its cognate
relatively low-shear venular part of the circulatory system with antigen. One round of recirculation from blood to the lymph
the endothelial surface membrane (Fig. 11.1). HEVs carry many node stroma, to a lymphatic vessel, and then back to blood takes
unique adhesion molecules that enable the capture of passing about 1 day. Naïve lymphocytes continue recirculating until they
lymphocytes. They also have special intercellular connections either find their cognate antigen or die.
that facilitate penetration of the vessel walls by these emigrating
lymphocytes. It has been estimated that more than 50% of ACTIVATED LYMPHOCYTES DISPLAY SELECTIVE
incoming lymphocytes make transient contacts with the vascular TISSUE HOMING PATTERNS
lining in the lymph nodes and that as many as one passing cell
in four adheres to the endothelium and then extravasates into In a secondary lymphoid organ, a successful encounter between
the tissue. a lymphocyte and its cognate antigen leads to the proliferation

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