Human dominant-negative class II transactivator transgenic pigs - effect on the human anti-pig T-cell immune response and immune status

Academic Article

Abstract

  • Swine leucocyte antigen (SLA) class II molecules on porcine (p) cells play a crucial role in xenotransplantation as activators of recipient human CD4+ T cells. A human dominant-negative mutant class II transactivator (CIITA-DN) transgene under a CAG promoter with an endothelium-specific Tie2 enhancer was constructed. CIITA-DN transgenic pigs were produced by nuclear transfer/embryo transfer. CIITA-DN pig cells were evaluated for expression of SLA class II with/without activation, and the human CD4+ T-cell response to cells from CIITA-DN and wild-type (WT) pigs was compared. Lymphocyte subset numbers and T-cell function in CIITA-DN pigs were compared with those in WT pigs. The expression of SLA class II on antigen-presenting cells from CIITA-DN pigs was significantly reduced (40-50% reduction compared with WT; P < 0·01), and was completely suppressed on aortic endothelial cells (AECs) even after activation (100% suppression; P < 0·01). The human CD4+ T-cell response to CIITA-DN pAECs was significantly weaker than to WT pAECs (60-80% suppression; P < 0·01). Although there was a significantly lower frequency of CD4+ cells in the PBMCs from CIITA-DN (20%) than from WT (30%) pigs (P < 0·01), T-cell proliferation was similar, suggesting no significant immunological compromise. Organs and cells from CIITA-DN pigs should be partially protected from the human cellular immune response. © 2013 John Wiley & Sons Ltd.
  • Published In

  • Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Hara H; Witt W; Crossley T; Long C; Isse K; Fan L; Phelps CJ; Ayares D; Cooper DKC; Dai Y
  • Start Page

  • 39
  • End Page

  • 46
  • Volume

  • 140
  • Issue

  • 1