title: Differential expression of lymphocyte homing receptors by human memory/effector T cells in pulmonary versus cutaneous immune effector sites.
abstract: The heterogeneous expression of lymphocyte homing receptors (HR) by the (CD45RA(low)/RO(high)) memory/effector T cell population in the human is thought to define subsets with tissue-selective recirculatory potential. To investigate further the localization characteristics of these T cells, we used multiparameter flow cytometry to quantitate T cell subsets defined by expression of the skin-selective HR called the cutaneous lymphocyte-associated antigen (CLA), the peripheral lymph node (PLN) HR L-selectin, the mucosal-associated HR alpha 4 beta 7-integrin, and the mucosal-associated adhesion molecule alpha e beta 7-integrin in either cutaneous or pulmonary immune effector sites and corresponding peripheral blood. Compared to peripheral blood, skin T cells were highly enriched for the CLA+/L-selectin+/alpha e beta 7-integrin- memory/effector subset, whereas lung memory/effector T cells were predominantly CLA-to low L-selectin-, and almost half were alpha e beta 7-integrin+. alpha 4 beta 7-integrin expressing memory/effector T cells were diminished in both skin and lung, suggesting that this HR is not a major participant in determining localization specificity in either of these sites. The characteristic pulmonary T cell HR phenotype did not significantly differ between the normal subjects and those with pulmonary inflammatory disease, and did not correlate with markers of T cell activation. Induction of a rapid up-regulation of pulmonary inflammation via intrabronchial allergen challenge in asthmatic patients tended to decrease localization specificity, resulting in a more general importation of memory/effector subsets. Taken together, these results suggest that tissue microenvironments play a major role in determining the character of local T cell infiltrates via their ability to import and retain memory/effector subsets selectively or, more generally, depending on the intensity of local inflammatory stimuli.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.
authors.forename: L J
authors.initials: LJ
authors.lastname: Picker
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Trumble
authors.forename: L S
authors.initials: LS
authors.lastname: Newman
authors.forename: P A
authors.initials: PA
authors.lastname: Collins
authors.forename: P R
authors.initials: PR
authors.lastname: Bergstresser
authors.forename: D Y
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016023:Integrins / Q000096:biosynthesis; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D008168:Lung / Q000276:immunology*; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D015815:Cell Adhesion Molecules; D016023:Integrins; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; C070709:integrin alphaEbeta7; D019041:L-Selectin; D017493:Leukocyte Common Antigens