Endothelial induction of the T-cell chemokine CCL21 in T-cell autoimmune diseases.
The signals that mediate T-cell infiltration during T-cell autoimmune diseases are poorly understood. The chemokine CCL21 (originally isolated by us and others as Exodus-2/6Ckine/SLC/TCA4) is highly potent and highly specific for stimulating T-cell migration. However, it is thought to be expressed only in secondary lymphoid organs, directing naive T cells to areas of antigen presentation. It is not thought to play a role in T-cell effector function during a normal immune response. In this study we tested the expression of T-cell chemokines and their receptors during T-cell autoimmune infiltrative skin diseases. By using immunohistology it was found that the expression of CCL21 but not CCL19 or 20 was highly induced in endothelial cells of T-cell autoimmune diseases. The receptor for CCL21, CCR7, was also found to be highly expressed on the infiltrating T cells, most of which expressed the memory CD45Ro phenotype. These data imply that the usual loss of CCL21 responsiveness in the normal development of memory T-cell effector function does not hold for autoimmune skin diseases.
Christopherson
Kent W
KW
Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202, USA.
Hood
Antoinette F
AF
Travers
Jeffrey B
JB
Ramsey
Heather
H
Hromas
Robert A
RA
D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens; D008010:Lichen Planus / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014699:Venules / Q000473:pathology
C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens