The role of lymphocytes in human dermal wound healing

Animal experimental data indicate a requirement for functionally active T lymphocytes to allow optimal healing of dermal wounds. Little evidence exists to confirm that this is the case in humans. Lymphocyte involvement in regulation of healing is probably mediated by release of secreted cytokines/growth factors, and we hypothesize that the cytokine profile requirement will be modulated as healing progresses. As this is likely to be reflected in lymphocyte subset changes over the course of normal healing, we investigated the immunophenotype of lymphocyte subpopulations during wound healing. Sequential biopsies were taken over 42 days from the margin of 12 wounds healing by secondary intention after pilonidal sinus excision. Serial biopsy sections were analysed by immunohistochemistry using lymphocyte-specific monoclonal antibodies, and lymphocytes were counted microscopically. Within 42 days, the mean decrease in wound volume was 87.5%. This was accompanied by significant changes in the wound margin lymphocyte population. Total numbers (mean +/- SEM) of T lymphocytes decreased from 36.8 +/- 9.8 cells per field at inclusion in the study to 25.9 +/- 3.0 immediately prior to wound closure, with a concomitant increase in B lymphocytes from 1 +/- 0.4 to 9.5 +/- 3.6 cells per field. The CD4/CD8 T-lymphocyte ratio fell from an initial level of 3.6 +/- 0.3 to 2.1 +/- 0.3 (mean +/- SEM) prior to closure. These data indicate that human wound-associated lymphocyte populations are modulated during healing; the increase in numbers of CD8+ T-suppressor lymphocytes is in accordance with previous animal data, indicating a role for these cells in downregulating healing as the wound closes. This study also documents an associated increase in B lymphocytes and healing of human wounds, with an as yet undefined role.