The potential role of the lymphocyte in fetal wound healing

Wound healing is a complex process involving a number of different cell populations. Since fetal wounds contain only a small number of mononuclear cells and no fibrosis immuno-histochemical techniques using monoclonal antibodies specific to T and B lymphocytes, as well as macrophages, were used to identify the mononuclear cells in fetal wounds and to compare the lymphocyte response with the adult wound healing response. Polyvinyl alcohol sponges were placed subcutaneously in fetal rabbits on day 24 of gestation (then 31 days). Adult rabbits underwent similar implantation. Implants (8 to 14 per group) were harvested 5 days later and examined by H&E and trichrome staining as well as immuno-histochemical staining with monoclonal antibody (Mab) specific for rabbit T and B lymphocytes. The sponges in one group of fetal rabbits were impregnated with the polypeptide growth factor, transforming growth factor-β (TGF-β), a known regulator of adult tissue repair. Adult wounds showed an intense inflammatory response with extensive collagen deposition; 80% of the infiltrating cellular elements were T lymphocytes. Fetal wounds were less cellular with minimal collagen deposition; 40% of the cells were T lymphocytes. The fetal wounds treated with TGF-β were intensely cellular and fibrotic with 71% of the cellular infiltrate comprised of T lymphocytes. The increased cellularity of the TGF-β wounds appears to be primarily the result of increased numbers of T lymphocytes. These findings demonstrate that the fetus mounts an attenuated T lymphocyte response compared to the adult. The increased response of T lymphocytes with TGF-β suggests that the specific growth factor milieu may account for the fetal response to wounding. These results provide additional evidence that T lymphocytes modulate the degree of wound fibroplasia and suggest that the fibrotic response to TFG-β in fetal wounds is at least in part mediated by T lymphocytes.