Immuno-inflammatory cell dynamics during cutaneous wound healing

Abstract

The process of wound healing begins with an inflammatory reaction that is principally dependent on cellular immune elements. Although the involvement in wound healing of leucocytes that mediate nonspecific immunity (e.g. neutrophils and macrophages) is well known, the participation of cells which prime the immune reaction, i.e. the lymphocytes, requires further investigation. This study was performed to examine the temporal sequence and kinetics of these cells during cutaneous wound repair. The model selected was a full-thickness skin excisional wound made on the flanks of female Wistar rats. At time points ranging from 3 h to 2 wk wound samples were processed for polyester wax-embedding. Target antigens were identified and monitored quantitatively in sections stained immunohistochemically. Monoclonal antibodies against neutrophils, macrophages, pan T cells and cytotoxic populations of lymphocytes were used. The results showed that these cells are involved in the process of wound healing in a distinctive dynamic pattern. The accumulation of CD3⁺ T lymphocytes in the wound bed was mainly associated with the phase of granulation tissue formation. Intraepithelial CD3⁺ T lymphocytes were detected in considerable numbers within the regenerating epidermis. The cytotoxic cell populations (OX8⁺ ) were classified morphologically into the cytotoxic/suppressor subset of T cells and NK cells. The OX8⁺ T cells were shown to have a kinetic pattern similar to CD3⁺ T lymphocytes but of a lower magnitude. The accumulation of OX8⁺ NK cells was confined to the early inflammatory phase of repair. It is concluded that CD3⁺ T lymphocytes as well as OX8⁺ cytotoxic populations of the immune system are involved in the process of cutaneous wound healing in temporal sequences which suggest that they may be involved in its modulation.