The interferon inhibiting cytokine IK is overexpressed in cutaneous T cell lymphoma derived tumor cells that fail to upregulate major histocompatibility complex class II upon interferon-gamma stimulation.
Cutaneous T cell lymphomas are characterized by an accumulation of malignant clonal lymphocytes in the skin and occasionally in the blood. We compared gene transcription profiles from cultured clonal lymphocytes with autologous healthy blood lymphocytes by microarray hybridization. Cutaneous T cell lymphoma derived cells transcribed high amounts of an interferon inhibiting cytokine factor. The presence of an interferon inhibiting cytokine factor was confirmed in 12 skin biopsies of mycosis fungoides and Sézary syndrome derived blood lymphocytes by reverse transcriptase-polymerase chain reaction. The presence of interferon inhibiting cytokine factor mRNA in Sézary syndrome derived lymphocytes was associated with a lack of HLA class II upregulation after stimulation with interferon-alpha and interferon-gamma. This was not due to a loss of the interferon signaling cascade as the presence of interferon-signaling components was confirmed by reverse transcriptase--polymerase chain reaction on the transcriptional level. The elevated constitutive interferon inhibiting cytokine factor expression observed in cutaneous T cell lymphoma derived cells was insensitive to interferon-gamma stimulation, but was enhanced in normal peripheral blood mononuclear cells. We suggest that interferon inhibiting cytokine factor contributes to the lack of HLA class II upregulation in lymphoma cells. Interferon inhibiting cytokine factor may participate in providing a microenvironment at the tumor site insensitive to interferon-gamma stimulation and thus prevents an efficient local immune response.
Willers
J
J
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
Häffner
A
A
Zepter
K
K
Storz
M
M
Urosevic
M
M
Burg
G
G
Dummer
R
R
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017471:Receptors, Interferon / Q000032:analysis; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C090444:IK protein, human