The homing mechanisms that bring naive T cells into lymph nodes are very efficient, resulting in a net flux of lymphocytes through lymph nodes that is estimated to be up to 25 × 10⁹ cells each day. On average, every naive T lymphocyte in the body goes through at least one node once a day. Peripheral tissue inflammation, which usually accompanies infections, increases the blood flow into lymph nodes draining the affected tissue and consequently increases T-cell influx into those lymph nodes. At the same time, the egress of the T cells into efferent lymphatics is transiently reduced by mechanisms we will discuss later, so that T cells stay in lymph nodes that drain sites of inflammation longer than in other lymph nodes. Protein antigens are concentrated in the lymph nodes and other secondary lymphoid organs, where they are presented to T cells by DCs, the type of APCs best able to initiate responses of naive T cells. Thus, movement and transient retention of naive T cells in the secondary lymphoid organs, together with the capture and con centration of antigens, maximize the chances of T-cell activation and initiation of adaptive immune responses.

The homing of naive T cells into lymph nodes and mucosa associated lymphoid tissues (MALTs) occurs through specialized postcapillary HEVs located in the T-cell zones. Naive T lymphocytes are delivered to secondary lymphoid tissues through arterial blood flow and they leave the circulation and migrate into the stroma of lymph nodes through these HEVs. HEVs are abundant in the outer part of the T-cell zone close to the B-cell follicle, a region known as the paracortex. These vessels are lined with plump endothelial cells and not the flat endothelial cells that are typical of other venules (Fig. 1). HEVs are also present in mucosal lymphoid tissues, such as Peyer patches in the gut, but not in the spleen. The endothelial cells of HEVs are specialized to display certain adhesion molecules and chemokines on their surfaces, discussed later, which support the selective homing of only certain populations of lymphocytes. Certain cytokines, such as lymphotoxin, are required for HEV development. In fact, HEVs may develop at extralymphoid sites of chronic inflammation, where such cytokines are produced for prolonged periods.

Fig1. High endothelial venules (HEVs). (A) Light micrograph of HEVs in a lymph node, illustrating the tall endothelial cells. (B) Expression of L-selectin ligand on HEVs, stained with a specific anti body by the immunoperoxidase technique. (The location of the antibody is revealed by a brown reaction product of peroxidase, which is coupled to the antibody; see Appendix III for details.) The HEVs are abundant in the T-cell zone of the lymph node. (C) A binding assay in which lymphocytes are incubated with frozen sections of a lymph node. The lymphocytes (stained dark blue) bind selectively to HEVs. (D) Scanning electron micrograph of an HEV with lymphocytes attached to the luminal surface of the endothelial cells. A, Courtesy Dr. Steve Rosen, Department of Anatomy, University of California, San Francisco. B, Courtesy Drs. Steve Rosen and Akio Kikuta, Department of Anatomy, University of California, San Francisco. C, Courtesy Dr. Steve Rosen, Department of Anatomy, University of California, San Francisco. D, Courtesy J. Emerson and T. Yednock, University of California, San Francisco, School of Medicine. From Rosen SD, Stoolman LM. Potential role of cell surface lectin in lymphocyte recirculation. In: Olden K, Parent J, eds. Vertebrate Lectins. Van Nostrand Reinhold; 1987.

Naive T-cell migration out of the blood through the HEVs into the lymph node parenchyma involves the adhesion molecules L-selectin and LFA-1 and the chemokine receptor CCR7. This process includes the sequential events described earlier for migration of all leukocytes (see Fig. 2), but migration across HEVs into lymphoid tissues involves particular adhesion molecules and chemokines that are not involved in the migration into nonlymphoid tissues (Fig. 3).

Fig2. Multistep leukocyte-endothelial interactions mediating leukocyte recruitment into tissues. (1) Production of cytokines at site of infection and tissue injury. (2) Selectin-mediated rolling of leukocytes. (3) Increase in integrin affinity. (4) Integrin-mediated firm attachment of leukocytes to endothelium. (5) Transmigration of leukocytes through endothelium. (6) Migration of leukocytes to site of infection and tis sue injury. IL-1, Interleukin-1; TNF, tumor necrosis factor.

Fig3. Molecules involved in migration of naive and effector T lymphocytes. (A) Naive T lymphocytes home to lymph nodes as a result of L-selectin binding to peripheral node addressin (PNAd) on high endothelial venules (HEVs), which are present only in secondary lymphoid organs, and as a result of binding chemokines (CCL19 and CCL21) displayed on the surface of the HEV by glycosaminoglycans. Activated T lymphocytes, including effector cells, home to sites of infection in peripheral tissues, and this migration is mediated by E-selectin and P-selectin, integrins, and chemokines that are produced at sites of infection. Additional chemokines and chemokine receptors, besides the ones shown, are involved in effector/memory T-cell migration. (B) The adhesion molecules, chemokines, and chemokine receptors involved in naive and effector/memory T-cell migration are described. ICAM-1, Intercellular adhesion molecule 1; LFA-1, leukocyte function–associated antigen 1; VCAM-1, vascular cell adhesion molecule 1; VLA-4, very late antigen 4.

• The rolling of naive T cells on HEVs in secondary lymphoid organs is mediated by L-selectin on the lymphocytes binding to PNAd on the HEV. PNAd is a 6-sulfo sialyl Lewis X carbohydrate attached to a glycoprotein backbone. The PNAd carbohydrate group that binds L-selectin may be attached to different sialomucins on the HEVs in different tissues. For example, on lymph node HEVs, the L-selectin ligand is dis played by two sialomucins, called glycan-bearing cell adhesion molecule 1 (GlyCAM-1) and CD34. In Peyer patches in the intestinal wall, the L-selectin ligand is exhibited on a glycoprotein called MAdCAM-1, which is also the ligand for the α4 β7 integrin.

 • As with leukocyte migration in other sites, the subsequent firm adhesion of naive T cells to the HEVs is mediated by integrins and their ligands, mainly LFA-1 on the T cells bind ing to ICAM-1 on the HEV endothelial cells.

• The principal chemokines that activate the naive T-cell integrins to a high-affinity state are CCL19 and CCL21, which are uniquely involved in leukocyte homing to T-cell zones of lymphoid tissues (see Chapter 2). The main sources of CCL19 and CCL21 are fibroblast reticular cells (FRCs) within the T-cell zone; CCL21 is also produced by HEVs. These chemokines are displayed on the surface of HEVs and recognized by rolling lymphocytes. Both these chemokines bind to the chemokine receptor CCR7, which is expressed at high levels on naive T cells. This interaction of the chemokines with CCR7 ensures that naive T cells increase integrin avidity and are able to adhere firmly to HEVs. Recall that CCR7 also governs DC migration via lymphatics into lymph nodes. The important role of L-selectin and chemokines in naive T-cell homing to secondary lymphoid organs is supported by many different experimental observations. Lymphocytes from L-selectin knockout mice do not bind to peripheral lymph node HEVs and the mice have a marked reduction in the number of lymphocytes in lymph nodes. Very few naive B or T cells are in the lymph nodes of mice with genetic deficiencies in CCL19 and CCL21 or CCR7.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تباشر تنفيذ المرحلة الثالثة من أعمال التوسعة

بمحافظة ذي قار.. قسم الشؤون الفكرية يقيم ندوة معرفية عن دور بصيرة العلماء في سلامة المجتمع

لأكثر من 180 طالبة.. مركز الثقافة الأسرية ينظم برنامج ربيع الثقافة المعرفي في بغداد

بحضور متوليها الشرعي.. العتبة العباسية المقدسة تطلق المرحلة الثالثة من القرعة العلنية لتوزيع قطع أراضي مدينة القمر السكنية لمنتسبيها

المزيد

الآخبار الصحية

سرّ بسيط لصحة القلب.. أطعمة تخفض الكوليسترول خلال أسابيع

سبب خفي لإعتام عدسة العين ؟

عوامل خفية تسرّع شيخوخة الدماغ

أسباب الرغبة الشديدة في تناول الحلويات والأطعمة النشوية

المزيد

الآخبار التكنلوجية

كندا تصنع كاسحة جليد من جيل جديد

رواد "أرتيميس 2" يكشفون تفاصيل حياتهم في الفضاء

حفريات صينية تكشف كائنات بحرية عاشت قبل 546 مليون عام

روسيا تطلق صاروخ "سويوز-2.1 إيه" من قاعدة بليسيتسك الفضائية

المزيد

مواضيع ذات صلة

The Major Proinflammatory Cytokines of Innate Immunity

Migration of Neutrophils and Monocytes to Sites of Infection or Tissue Injury

Leukocyte-Endothelial Interactions and Leukocyte Recruitment into Tissues

Formation of Pus

Feedback Control of the Macrophage and Neutrophil Responses

Macrophage and Neutrophil Responses During Inflammation

Natural Killer Cells

Integrins and Integrin Ligands

Selectins and Selectin Ligands

Anatomy and Functions of Lymphoid Tissues : Spleen

Eosinophils

Phagocytosis