Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

Abstract

T lymphocytes bearing the γδ-TCR accumulate during wound healing and inflammation. However, the role of γδ-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human γδ-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 γδ-T cells was used as a model to evaluate the regulation of CTGF gene expression. Blood γδ-T cells isolated from healthy donors were grown in the presence of IL-15/TGF-β1 for 48 h and assessed for the expression and synthesis of CTGF. Nonstimulated human blood γδ-T cells and Loucy γδ-T cells expressed low levels of CTGF mRNA. Costimulation of the cells with IL-15 and TGF-β1 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+ αβ-T cells were analyzed. In addition, Western blot analysis of human γδ-T cell lysates prepared 4 days following stimulation with IL-15 and TGF-β1 revealed a 38-kDa CTGF protein in cell lysates of human γδ-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+ αβ-T cells human γδ-T cells are capable of expressing CTGF mRNA and synthesizing its corresponding protein, which supports the concept that γδ-T cells may contribute to wound healing or tissue fibrotic processes.

Transforming Growth Factor Beta-Induced Connective Tissue Growth Factor and Chronic Allograft Rejection

“…It should be noted that human c d, but not ab T cells have been shown to produce CTGF in response to TGFb and IL-15 (45). In addition, NK cells, which may respond to MHC disparate allografts, have recently been shown to play a role in CR (46).…”

Immunophenotyping and Protein Profiling of Fontan-associated Plastic Bronchitis Airway Casts

“…This is unexpected because the lymphocyte population of the airways is similar to that of the systemic circulation (29) and the immune response is not only important in inflammation but is essential for its resolution (30)(31)(32)(33). Much attention has been paid to the role of neutrophils and macrophages, particularly regarding acute inflammation (34).…”

Connections between Warburg’s and Szentgyorgyi’s Approach about the Causes of Cancer

“…T-cells, macrophages, and NKcells migrate to the injured tissue to remove the debris and the injured cells. The T-cells, the monocytes and the macrophages present growth-and repair factors [68][69][70]. The GR genes activate the neighboring cells (bystander effect), which also give out GR factors.…”

“…However, in the case of any damage, some cells produce such a functional state which repairs the actual dysfunction. The growth-or repairing-phase special genes are activated to produce such cells, which repair the damaged tissue [69,68]. Growth and reparative factors are released [71,72].…”