Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis.
We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.
Wu
K D
KD
Department of Dermatology, Marselisborg Hospital, University of Aarhus, 8000 Aarhus C, Denmark. wuk@mskcc.org
Hansen
E R
ER
D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000502:physiology; D015139:Blotting, Southern; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D010267:Parapsoriasis / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D012016:Reference Values; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D019098:Telomerase