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The Journal of Immunology, 2003, 170: 153-157.
Copyright © 2003 by The American Association of Immunologists

Human {gamma}{delta}-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-{beta}1 and Comparison with {alpha}{beta}-T Lymphocytes1

Grefachew Workalemahu2, Martin Foerster, Claus Kroegel and Ruedi K. Braun

Pneumology and Allergology, University Medical Clinic IV, Jena, Germany

T lymphocytes bearing the {gamma}{delta}-TCR accumulate during wound healing and inflammation. However, the role of {gamma}{delta}-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human {gamma}{delta}-T cells express and synthesize connective tissue growth factor (CTGF), a factor known to regulate fibrogenesis and wound healing. In addition, the lymphoblastic leukemia T cell line (Loucy) that possesses characteristics typical of {gamma}{delta}-T cells was used as a model to evaluate the regulation of CTGF gene expression. Blood {gamma}{delta}-T cells isolated from healthy donors were grown in the presence of IL-15/TGF-{beta}1 for 48 h and assessed for the expression and synthesis of CTGF. Nonstimulated human blood {gamma}{delta}-T cells and Loucy {gamma}{delta}-T cells expressed low levels of CTGF mRNA. Costimulation of the cells with IL-15 and TGF-{beta}1 resulted in a substantially increased level of CTGF mRNA expression within 4–8 h, and it remained elevated for at least 48 h. In contrast, no CTGF mRNA was detected when nonstimulated and stimulated human CD4+ {alpha}{beta}-T cells were analyzed. In addition, Western blot analysis of human {gamma}{delta}-T cell lysates prepared 4 days following stimulation with IL-15 and TGF-{beta}1 revealed a 38-kDa CTGF protein in cell lysates of human {gamma}{delta}-T cells. Detection was confirmed using Colo 849 fibroblasts, which can constitutively express high levels of CTGF. In conclusion, we herein present novel evidence that in contrast to CD4+ {alpha}{beta}-T cells human {gamma}{delta}-T cells are capable of expressing CTGF mRNA and synthesizing its corresponding protein, which supports the concept that {gamma}{delta}-T cells may contribute to wound healing or tissue fibrotic processes.




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