Absence of CD4 or CD8 lymphocytes changes infiltration of inflammatory cells and profiles of cytokine expression in skin wounds, but does not impair healing

Abstract

The involvement of lymphocytes in skin wound healing has not been studied extensively. This study shows that CD4 and CD8 cells are present in significant numbers in skin wounds with peak levels at days 5-10 and 7-10, respectively. Both subsets expressed inflammatory and/or regulatory cytokines. To examine the function of CD4 and CD8 lymphocytes in tissue repair, wound healing was examined in mice deficient for either CD4 or CD8 cells. Wounds in CD4 deficient mice exhibited an initial delayed infiltration of CD8 cells followed by a relative increase in CD8 cells at day 10 and thereafter. Wounds in CD4 deficient mice also displayed up-regulated expression of IL1β, IL-6, IL-17, IFN-γ, CXCL-1 and down-regulated expression of IL-4 as compared to wild-type mice. In contrast, wounds in CD8 deficient mice showed significantly decreased infiltration of CD4+ cells, neutrophils, and macrophages along with down-regulated expression of IL1β, IL-6, TNF-α, CXCL-1, CCL-2 and up-regulated expression of IL-4 as compared to wild-type mice. Despite these significant changes in cytokine expression and inflammatory cell infiltrate, the rate of wound closure, wound breaking strength, collagen content and angiogenesis in either CD4 or CD8 deficiency showed no significant difference from that of wild-type mice. The results suggest that, despite being present and involved in wound inflammation, neither CD4+ nor CD8+ cells play critical roles in the healing process of skin wounds. Further studies are needed to investigate whether these cells might play critical roles in wounds that experience stress such as ischemia or infection.

Keywords: CD4; CD8; skin; wound.