The relationship between interferon-γ and keratinocyte alloantigen expression after burn injury

Background: Cultured keratinocyte (CK) and cadaveric skin allografts have prolonged survival in patients with massive thermal injury. It is unclear if this delayed rejection is due to impaired host responsiveness or decreased graft immunogenicity. Although burn injury has been shown to decrease parameters of allograft response, no studies have examined the effect of burn injury on alloantigen expression. This study investigated the effect of burn size on class II antigen expression in CK allografts as well as on tissue levels of interferon-γ (IFN-γ), the principle regulator of alloantigen expression. Methods: Anesthetized CBA mice (n = 64) received a 0%, 20% partial-thickness (PT), 20% full-thickness (FT), or 40% FT contact burn. Forty-eight hours later, wounds were partially excised and covered with CK allografts from C57BL/6 donors. Five days after burn injury, grafts were analyzed for donor-specific class II antigen. Protein expression was determined by Western immunoblotting and quantified with video densitometry. Wound, serum, and unburned skin levels of IFN-γ were determined by enzyme- linked immunosorbent assay. Groups were compared by Fisher's analysis of variance. Results: As burn size increased, class II antigen expression decreased (p < 0.001). This corresponded with decreased wound and skin levels of IFN-γ after 40% burn (p < 0.05); however, wound IFN-γ was significantly elevated after 20% PT and FT burns (p < 0.01). Serum IFN-γ increased as burn size increased (p < 001). Conclusions: Burn injury decreases the antigenicity of CK allografts, which partly explains delayed allograft rejection after burn injury. Although wound IFN-γ increases after minor thermal injury, the profound decrease in wound and skin IFN-γ after a major burn corresponds with diminished class II antigen expression. The decreased availability of IFN-γ after major thermal injury provides a mechanism for limited allograft tolerance.