Mucosaassociated Lymphoid Tissues

Specialized lymphoid compartments underlie mucosal surfaces of the gut and bronchial epithelium. Lymphoid follicles which occur just beneath the epithelium throughout the small intestine and are known as Peyer patches. A subset of intestinal epithelial cells known as M cells are specialized for transport of bacteria and other antigens from the intestinal lumen to the Peyer patches where antigen-dependent B cell differentiation occurs (5).

Figure 8 The binding of CLA on memory T cells to E-selectin and P-selectin on the luminal surface of cutaneous postcapillary venules initiates the process known as tethering. Tethering slows the movement of T lymphocytes which then upregulate expression of integrins a1b2 (LFA-1) and a4b1 (VLA-4) which bind to VCAM-1 and ICAM-1, respectively on the luminal surface of endothelial cells (8,9). Following tethering, the T lymphocytes become flattened on the endothelial cell surface in preparation for extravasation though the endothelial layer. (Reproduced from Fig. 2 of Ref. 4, Copyright 1999, Massachusetts Medical Society, all rights reserved.)

Figure 8 The binding of CLA on memory T cells to E-selectin and P-selectin on the luminal surface of cutaneous postcapillary venules initiates the process known as tethering. Tethering slows the movement of T lymphocytes which then upregulate expression of integrins a1b2 (LFA-1) and a4b1 (VLA-4) which bind to VCAM-1 and ICAM-1, respectively on the luminal surface of endothelial cells (8,9). Following tethering, the T lymphocytes become flattened on the endothelial cell surface in preparation for extravasation though the endothelial layer. (Reproduced from Fig. 2 of Ref. 4, Copyright 1999, Massachusetts Medical Society, all rights reserved.)

Memory T cells are generated in lymph nodes draining the skin and recirculate back to the skin during inflammation or certain pathologic conditions, e.g., cutaneous T-cell lymphoma. The process of homing to the skin requires the binding of memory T cells to specialized receptors on endothelial cells (Fig. 8). The process of skin homing is mediated by CLA, a specialized form of P-selectin glycoprotein ligand expressed on the tips of microvilli of skin-homing T cells (6). Expression of CLA is critically dependent upon signals from the microenvironment, being upregulated by transforming growth factor-beta and to a lesser degree by interleukin-6 (7). Upon reaching the extravascular space, T cells are subject to chemotactic stimuli from sites of injury or infection. When exposed to antigen, they become activated and release inflammatory cytokines (chemokines) which amplify the inflammatory infiltrate. Chemokines are small (8-10 kDa) chemotactic cytokines, that act through G-pro-tein-coupled receptors and are classified by the spacing of the cysteine residues near the amino terminus (10). The differential expression of chemokines and their receptors most likely contributes to the characteristic histopathology, anatomic sites of origin, and spread of lymphoproliferative disorders (11).

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