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

C. C. Blackburn, J. L. Grogan, C. L. Augustine, J. F.A.P. Miller, G. Varigos, G. Morahan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 responses. Peripheral tolerance to skin antigens was not broken by in situ IL-2 expression because syngeneic KIL-2 skin grafts were not rejected. However, MHC Class I-disparate skin grafts from KIL-2 donors were rejected faster (median 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 graft rejection (MST 14 days) did not differ significantly from controls (MST 16 days), suggesting that upregulation of IL-2 at the effector site could affect CD4+ T cell-independent, but not CD4+ T cell-dependent, responses. No effect on rejection kinetics was observed when wild type allogeneic skin was grafted onto transgenic mice that expressed bc12 constitutively in their lymphocytes (MST of 14 days, both sets), indicating that this was not 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.

Original languageEnglish
Pages (from-to)128-131
Number of pages4
JournalImmunology & Cell Biology
Issue number2
Publication statusPublished - 19 Apr 2001

Keywords / Materials (for Non-textual outputs)

  • Cytokine
  • Interleukin-2
  • Skin graft


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