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 lymphocytes.
T lymphocytes bearing the gammadelta-TCR accumulate during wound healing and inflammation. However, the role of gammadelta-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human gammadelta-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 gammadelta-T cells was used as a model to evaluate the regulation of CTGF gene expression. Blood gammadelta-T cells isolated from healthy donors were grown in the presence of IL-15/TGF-beta1 for 48 h and assessed for the expression and synthesis of CTGF. Nonstimulated human blood gammadelta-T cells and Loucy gammadelta-T cells expressed low levels of CTGF mRNA. Costimulation of the cells with IL-15 and TGF-beta1 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+ alphabeta-T cells were analyzed. In addition, Western blot analysis of human gammadelta-T cell lysates prepared 4 days following stimulation with IL-15 and TGF-beta1 revealed a 38-kDa CTGF protein in cell lysates of human gammadelta-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+ alphabeta-T cells human gammadelta-T cells are capable of expressing CTGF mRNA and synthesizing its corresponding protein, which supports the concept that gammadelta-T cells may contribute to wound healing or tissue fibrotic processes.
Workalemahu
Grefachew
G
Pneumology and Allergology, University Medical Clinic IV, Jena, Germany. grefachew.workalemahu@med.uni-jena.de
Foerster
Martin
M
Kroegel
Claus
C
Braun
Ruedi K
RK
D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D055513:Connective Tissue Growth Factor; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D019409:Interleukin-15 / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor