Am. J. Respir. Cell Mol. Biol., Volume 19, Number 6, December, 1998 892-900

Human Airway Epithelial Monolayers Promote Selective Transmigration of Memory T Cells: A Transepithelial Model of Lymphocyte Migration into the Airways

Lisa A. Miller and Eugene C. Butcher

Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California at Davis, Davis; and Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, Stanford, California

It has previously been demonstrated that T lymphocytes in the conducting airways express a pattern of adhesion molecules that are uniquely different from T lymphocytes found circulating in peripheral blood. To examine the role of airway epithelia in the determination of migratory capacity for human monocyte and lymphocyte populations in vivo, we have developed an in vitro transepithelial migration model using the human transformed bronchial epithelial cell line BEAS-2B S.6. In this study, we have demonstrated the preferential migration of human peripheral blood mononuclear cells (PBMC) across BEAS-2B S.6 cell monolayers in a physiologically appropriate direction (basal to apical epithelial cell surface). Stimulation of BEAS-2B S.6 cells with a combination of interferon- and tumor necrosis factor- upregulated basal-to-apical transepithelial migration by at least twofold. Monocytes migrated most efficiently, but subpopulations of CD19⁺ B cells and CD2⁺ cells were also recruited across epithelial cell monolayers. In the T lymphocyte subset of PBMC, CD45RO⁺ "memory" cells migrated preferentially. In addition, CD4⁺ cells exhibited a significantly greater capacity to migrate across airway epithelium compared with CD8⁺ cells. Migrated CD4⁺ cells were predominantly CD29^high/CD26^high, and within this subset uniformly expressed CD62L (L-selectin) at an intermediate level. PBMC migration across BEAS-2B S.6 cells was significantly inhibited by pertussis toxin; this result implicates a G protein signaling event as an important mediator of lymphocyte/monocyte transepithelial migration. On the basis of these data, we conclude that bronchial epithelium provides a unique microenvironment that supports the selective, G protein-dependent migration of memory T cells.

This article has been cited by other articles:

				J. C. Porter, M. Falzon, and A. Hall Polarized Localization of Epithelial CXCL11 in Chronic Obstructive Pulmonary Disease and Mechanisms of T Cell Egression J. Immunol., February 1, 2008; 180(3): 1866 - 1877. [Abstract] [Full Text] [PDF]

				B. Saatian, X.-Y. Yu, A. P. Lane, T. Doyle, V. Casolaro, and E. Wm. Spannhake Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L217 - L225. [Abstract] [Full Text] [PDF]

				E. S. Schelegle, L. J. Gershwin, L. A. Miller, M. V. Fanucchi, L. S. Van Winkle, J. P. Gerriets, W. F. Walby, A. M. Omlor, A. R. Buckpitt, B. K. Tarkington, et al. Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae) Am. J. Pathol., January 1, 2001; 158(1): 333 - 341. [Abstract] [Full Text] [PDF]

				L. A. Miller, J. Usachenko, R. J. McDonald, and D. M. Hyde Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms J. Leukoc. Biol., August 1, 2000; 68(2): 201 - 208. [Abstract] [Full Text]

				J. S. ERJEFÄLT and C. G. A. PERSSON New Aspects of Degranulation and Fates of Airway Mucosal Eosinophils Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 2074 - 2085. [Full Text]