Lesional psoriatic T cells contain the capacity to induce a T cell activation molecule CDw60 on normal keratinocytes.
In this report we demonstrate, that in psoriatic skin, basal and suprabasal keratinocytes express CDw60. The CDw60-specific monoclonal antibody, UM4D4, has recently been shown to recognize the 9-O-acetylated disialosyl group on ganglioside GD3. The CDw60 antigen on cultured keratinocytes also seems to be identical with the 9-O-acetylated disialosyl group, because the anti-UM4D4 binding was markedly reduced after neuraminidase treatment of keratinocytes. To examine whether factors from T cells in psoriatic lesions are responsible for the overexpression of CDw60 on keratinocytes, T cell lines obtained from lesional skin were initiated and cloned by limiting dilution. Factors released from 19 of 19 activated T cell clones up-regulated CDw60 expression on cultured normal keratinocytes. T-cell-secreted cytokines, including interleukin (IL)-2, IL-3, IL-4, IL-6, IL-13, transforming growth factor-beta, granulocyte/macrophage colony-stimulating factor, and interferon-gamma were tested for their capacity to modulate keratinocyte CDw60 expression. IL-4 and IL-13 strongly up-regulated the expression of CDw60; by contrast, interferon-gamma down-regulated keratinocyte CDw60 expression. Interestingly, IL-13 may in part be responsible for the T-cell-induced up-regulation of CDw60, because anti-IL-13 partly neutralized this effect of the T cell supernatant. In conclusion, CDw60 expression on psoriatic epidermal keratinocytes is likely induced by intralesionally activated T cells and may in part be due to IL-13. These findings would represent a novel mechanism by which T cells participate in the pathogenesis of psoriasis.
Skov
L
L
Department of Dermatology, Gentofie Hospital, University of Copenhagen, Denmark.
Chan
L S
LS
Fox
D A
DA
Larsen
J K
JK
Voorhees
J J
JJ
Cooper
K D
KD
Baadsgaard
O
O
D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured; D002999:Clone Cells; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D008213:Lymphocyte Activation; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D012016:Reference Values; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C064741:CDw60 antigen; D016895:Culture Media, Serum-Free; D018793:Interleukin-13; D015847:Interleukin-4