Increased expression of CTLA-4 in malignant T-cells from patients with mycosis fungoides -- cutaneous T cell lymphoma.
Mycosis fungoides (MF) is a low-grade lymphoma of cluster of differentiation (CD)4+, CD45RO+, cutaneous leukocyte antigen (CLA)+ T cells that homes to the skin. To understand the functional abnormalities in this disease, we study the regulation of cytotoxic T-lymphocyte antigen (CTLA)-4 in peripheral blood mononuclear cells (PBMCs) from patients with MF. CTLA-4 is a costimulatory molecule for T cells that functions in immunoregulation. Unlike the expression of CD28, which is expressed constitutively on T cells, CTLA-4 expression is highly regulated. In the analysis of PBMCs in MF, we found that CTLA-4 is stimulated by phorbol myristate acetate/A23187 to a greater level when compared to normals. This defect was seen in the dominant clones of T cells. The increased CTLA-4 expression was significant between normal and MF, with a correlation between higher expression of CTLA-4 and a higher grade of MF. In a patient whose disease progressed, the CTLA-4 level increased. The abnormal level of CTLA-4 was confirmed at both the transcription and translation levels. Although MF is associated with a Th2 bias, Th1 cytokines IL-2 and IFN-gamma enhanced CTLA-4 expression, while IL-4 did not. These findings reveal an abnormal regulation of CTLA-4 expression in MF and show that PBMCs from patients with MF have properties that are divergent from those of normal T cells.
Wong
Henry K
HK
Department of Dermatology, Henry Ford Hospital, Detroit, Michigan 48202, USA. hwong1@hfhs.og
Wilson
Adam J
AJ
Gibson
Heather M
HM
Hafner
Mikehl S
MS
Hedgcock
Carrie J
CJ
Berger
Carole L
CL
Edelson
Richard L
RL
Lim
Henry W
HW
D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D012333:RNA, Messenger