Antigen receptor-stimulated peripheral blood and bronchoalveolar lavage-derived T cells induce MHC class II and ICAM-1 expression on human airway smooth muscle.
The current model of lymphocyte extravasation into areas of inflammation involves the sequential engagement of multiple cell adhesion molecules (CAMs) expressed on lymphocytes and endothelial cells. In addition, the expression of CAMs and the elaboration of matrix by subendothelial/submucosal cells may contribute to the retention and stimulation of infiltrating cells in an inflammatory lesion. We previously demonstrated that mitogen-activated T cells adhered to airway smooth muscle (ASM) in an integrin-dependent fashion. ASM are MHC class II-negative and expressed low basal levels of intercellular adhesion molecule-1 (ICAM-1). In this study, we demonstrate that anti-CD3-stimulated peripheral blood T cells also adhere to ASM and markedly upregulate ICAM-1 expression and induce the expression of MHC class II on ASM. The induction of HLA-DR was completely inhibited, and the induction of ICAM-1 partially inhibited, by neutralizing antibody against interferon-gamma. Furthermore, in studies with bronchoalveolar lavage-derived T cells isolated from atopic donors following local antigen challenge, we observed adhesion to ASM and upregulation of ASM expression of ICAM-1 and HLA-DR similar to that seen with in vitro-activated T cells. Finally, we found that despite expression of ICAM-1 and HLA-DR, ASM could not present alloantigen to CD4+ T cells. These findings suggest that the interaction of activated T cells with parenchymal cells of the lung such as airway smooth muscle affects the phenotype of myocytes and thus may have significant implications for inflammatory diseases such as asthma or transplant rejection.
Lazaar
A L
AL
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, USA.
Reitz
H E
HE
Panettieri
R A
RA
Peters
S P
SP
Puré
E
E
D017951:Antigen Presentation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D006680:HLA Antigens / Q000096:biosynthesis*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D009130:Muscle, Smooth / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014132:Trachea / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D017252:CD3 Complex; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma