Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.

Abstract

The tissue localization or "homing" of circulating lymphocytes is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. In peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches and appendix), and sites of chronic inflammation, for example, lymphocytes leave the blood by adhering to and migrating between those endothelial cells lining postcapillary high endothelial venules (HEV). Functional analyses of lymphocyte interactions with HEV have shown the lymphocytes can discriminate between HEV in different tissues, indicating that HEV express tissue-specific determinants or address signals for lymphocyte recognition. We recently described such a tissue-specific "vascular addressin" that is selectively expressed by endothelial cells supporting lymphocyte extravasation into mucosal tissues and that appears to be required for mucosa-specific lymphocyte homing (Streeter, P. R., E. L. Berg, B. N. Rouse, R. F. Bargatze, and E. C. Butcher. 1988. Nature (Lond.). 331:41-46). Here we document the existence and tissue-specific distribution of a distinct HEV differentiation antigen. Defined by monoclonal antibody MECA-79, this antigen is expressed at high levels on the lumenal surface and in the cytoplasm of HEV in peripheral lymph nodes. By contrast, although MECA-79 stains many HEV in the mucosal Peyer's patches, expression in most cases is restricted to the perivascular or ablumenal aspect of these venules. In the small intestine lamina propria, a mucosa-associated site that supports the extravasation of lymphocytes, venules do not stain with MECA-79. Finally, we demonstrate that MECA-79 blocks binding of both normal lymphocytes and a peripheral lymph node-specific lymphoma to peripheral lymph node HEV in vitro and that it also inhibits normal lymphocyte homing to peripheral lymph nodes in vivo without significantly influencing lymphocyte interactions with Peyer's patch HEV in vitro or in vivo. Thus, MECA-79 defines a novel vascular addressin involved in directing lymphocyte homing to peripheral lymph nodes.

Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses.

“…A recent study also indicates, although indirectly, a similar pattern of ␣4␤7 expression on ASC induced by diarrheal disease (35). It is possible that the ␣4␤7 ϩ and L-selectin Ϫ ASC are bound to extravasate through flat-walled venules in the intestinal lamina propria, which constitutively express MAdCAM-1 but only little PLN addressin (8,10,36). ␣4␤7 ϩ and L-selectin ϩ ASC, on the other hand, may leave the circulation and migrate to more organized mucosal lymphoid tissues, such as mesenteric lymph nodes (MLN) and Peyer's patches, whose HEV express both MAd-CAM-1 and PLN addressin (36,37), and to which L-selectindependent homing has been documented (38).…”

“…It is possible that the ␣4␤7 ϩ and L-selectin Ϫ ASC are bound to extravasate through flat-walled venules in the intestinal lamina propria, which constitutively express MAdCAM-1 but only little PLN addressin (8,10,36). ␣4␤7 ϩ and L-selectin ϩ ASC, on the other hand, may leave the circulation and migrate to more organized mucosal lymphoid tissues, such as mesenteric lymph nodes (MLN) and Peyer's patches, whose HEV express both MAd-CAM-1 and PLN addressin (36,37), and to which L-selectindependent homing has been documented (38). In accordance with this notion, our previous studies have shown that MLN harbor large numbers of vaccine-specific ASC after enteric immunization in monkeys (39).…”

Endothelial L-Selectin Ligands Are Likely to Recruit Lymphocytes into Rejecting Human Heart Transplants

“…As shown in Table 1, 2F3 and HECA-452 mAbs detect ␣2,3 sialylation and ␣1,3 fucosylation of lactosamine and do not distinguish between sulfation and nonsulfation. 29,30 On the other hand, MECA-79 needs sulfation of its epitope for proper recognition. 31,32 The best ligands, ie, ligands with highest relative binding affinity toward L-selectin, would possess all these decorations, as shown in lymphatic tissue.…”

“…30,31 This is actually a family of glycoproteins, most of which are able to bind L-selectin. In humans only CD34 and podocalyxin have been identified at molecular level among the glycoprotein species reacting with MECA-79.…”

Alternate Mucosal Immune System: Organized Peyer’s Patches Are Not Required for IgA Responses in the Gastrointestinal Tract

“…It is well established that the MLN drain lymphocytes from the intestine and it was shown that MLN possess features of both mucosal and peripheral lymphoid tissue in terms of lymphocyte trafficking (35,36). In this regard, high endothelial venules in MLN clonally express high levels of both mucosal addressin cell adhesion molecule-1 and peripheral LN addressin which are major mucosal and peripheral LN addressins, respectively (37). Further, mucosal as well as peripheral node cell lines have been shown to bind to high endothelial venules of MLN in vitro (38).…”