HUT 78 T cells bind to noncytokine-stimulated keratinocytes using a non-CD18-dependent adhesion pathway.
The initial in vitro observation that cultured keratinocytes, when treated with cytokines such as gamma interferon, increased the binding of T lymphocytes, opened up a whole new avenue of research to understand epidermal trafficking patterns in inflammatory skin diseases. A growing body of data strongly supports the in vivo role of lymphocyte-function-associated antigen-1 (CD18) expression by T cells in the binding to intercellular adhesion molecule-1 (CD54) expressing keratinocytes. To further explore the molecular basis for other possible adhesive interactions involving T cells and skin-derived cellular constituents, the authors used 2 cell lines (HUT 78 cells and Jurkat cells) and added them to multipassaged human keratinocytes, fibroblasts, and melanocytes. The skin-derived cells were treated with cytokines alone, or in combination, with a phorbol ester. HUT cells were capable of binding to keratinocytes in the absence of pretreatment with cytokines at 25 degrees C, which was not inhibited by anti-CD18 antibodies, or sensitive to reducing the temperature of the adhesion assay to 7 degrees C. Fibroblasts and melanocytes also constitutively bound HUT cells, but the binding to fibroblasts was highly temperature-sensitive. When keratinocytes were pretreated for 48 hours with gamma interferon plus phorbol ester, a "superadhesive" state was induced, resulting in a synergistically increased binding ability of both HUT cells and Jurkat cells. This effect was related to quantitative increases in keratinocyte intercellular adhesion molecule-1 expression. Several other clear-cut qualitative and quantitative differences were detectable in the ability of HUT cells and JS cells to bind to nontreated and cytokine/phorbol ester-treated keratinocytes, fibroblasts, and melanocytes. These results emphasize the complexity of molecular associations underlying T-cell trafficking patterns, potentially operative in the dermal and epidermal compartments of the skin.
Department of Pathology, University of Michigan Medical Center, Ann Arbor.
B J
BJ
Nickoloff
R S
RS
Mitra
Y
Y
Shimizu
J N
JN
Barker
G
G
Karabin
T
T
Stoof
L M
LM
Stoolman
D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004357:Drug Synergism; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D008544:Melanocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate