Effect of localized cytokine dysregulation: Accelerated rejection of IL-2-expressing skin grafts

Transgenic mice were created In which a sheep keratin promoter directed the expression of IL-2 into the dermis. These KIL-2 transgenic mice were used to investigate the effects of localized IL-2 dysregulation on immune respon ses, Peripheral tolerance to skin antigens was not broken by in situ IL-2 e xpression because syngeneic KIL-2 skin grafts were not rejected. However, M HC Class 1-disparate skin grafts from KIL-2 donors were rejected faster (me dian survival time (MST) 12 days) than grafts of non-transgenic littermate skin (MST 18 days), In contrast. the kinetics of KIL-2 H-Y-disparate skin g raft rejection (MST 14 days) did not differ significantly from controls (MS T 16 days), suggesting that upregulation of IL-2 at the effector site could affect CD4(-) T cell-independent. but not CD4(+) T cell-dependent, respons es. No effect on rejection kinetics was observed when wild type allogeneic skin was grafted onto transgenic mice that expressed bcl2 constitutively In their lymphocytes (MST of 14 days, birth sets), indicating that this was n ot simply due to Increased longevity of T cells within the IL-2 expressing graft. We therefore suggest that aberrant expression of IL-2 can accelerate helper-independent CD8(+) T cell responses by increasing proliferation and /or differentiation of cytolytic T cells at the effector site.