UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.
UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell activation pathway, was found to be highly expressed on lesional psoriatic T cells. To examine whether UM4D4 represents a T-cell activation pathway for psoriatic T cells, a T-cell line was initiated from an acute skin lesion and cloned by limiting dilution. Clonality was verified by analysis of T-cell receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-, CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were heterogeneous in the degree of anti-UM4D4-induced proliferation and in their production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4 activation were capable of inducing ICAM-1 and HLA-DR expression on cultured normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic skin provides an alternative mechanism for T-cell activation that may be operative in the psoriatic lesional milieu. Indeed, activation of lesional T-cells through the UM4D4 molecule resulted in release of lymphokines that directly induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.
Baadsgaard
O
O
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor 48109-0530.
Tong
P
P
Elder
J T
JT
Hansen
E R
ER
Ho
V
V
Hammerberg
C
C
Lange-Vejlsgaard
G
G
Fox
D A
DA
Fisher
G
G
Chan
L S
LS
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008222:Lymphokines / Q000378:metabolism*; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics / Q000473:pathology; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C064741:CDw60 antigen; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008222:Lymphokines; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma