Selective recognition of mucosal lymphoid high endothelium by gut intraepithelial leukocytes.
Circulating precursors of mucosal immunoglobulin A plasma cells and T-cell immunoblasts migrate selectively into mucosal sites from the blood, but the mechanisms controlling this selective trafficking have not been determined. One possibility is that the site-specific extravasation of circulating effector cell populations is determined by organ-specific endothelial cell recognition mechanisms. Here we have assessed the ability of isolated mouse gut intraepithelial lymphocytes to recognize and bind to mucosal versus nonmucosal lymphoid organ high endothelial venules, vessels that support high levels of lymphocyte traffic in vivo. In an in vitro assay of lymphocyte interaction with high endothelial venules in frozen sections, intraepithelial leukocytes bind well to high endothelial venules in Peyer's patches but, unlike most circulating B and T lymphocytes, are unable to interact with peripheral lymph node high endothelial venules. Furthermore, we show by in situ immunohistology and in cell suspension immunofluorescence studies that intraepithelial leukocytes fail to stain with a monoclonal antibody, MEL-14, against putative lymphocyte receptors for lymph node high endothelial venules. Thus, they lack a cell surface glycoprotein required for homing to peripheral nodes. The demonstration of organ-specific recognition of endothelial cells by a normal mucosal effector lymphocyte population suggests that selective interactions with endothelium may play an important role in controlling the distribution of effector cells in vivo. The utilization of organ-specific endothelial cell recognition mechanisms by circulating precursors of mucosal effector cells could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from nonmucosal immune mechanisms.
Schmitz
M
M
Department of Pathology, Stanford University Medical Center, California.
Nunez
D
D
Butcher
E C
EC
D000818:Animals; D004727:Endothelium / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D007413:Intestinal Mucosa / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D008221:Lymphoid Tissue / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014680:Veins / Q000502:physiology*; D014699:Venules / Q000502:physiology*