title: The effect of Gal expression on pig cells on the human T-cell xenoresponse.
abstract: BACKGROUND
  Lack of Gal expression on pig cells is associated with a reduced primate humoral immune response as well as a reduction in cytokine production by human cells in vitro. We investigated whether lack of Gal expression is associated with reduced human T-cell response in vitro.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) were obtained from healthy humans and naïve baboons. Human CD4+ and CD8+ T cells were isolated. Porcine aortic endothelial cells (pAECs) were isolated from wild-type (WT) and α1,3-galactosyltransferase gene-knockout (GTKO) pigs. WT pAECs were treated with α-galactosidase, reducing Gal expression. Swine leukocyte antigen (SLA) class I and II expression on pAECs was measured, as was T-cell proliferation and cytokine production in response to pAECs.
  
  
  RESULTS
  Reduced Gal expression on WT pAECs after α-galactosidase treatment was associated with reduced human PBMC proliferation (P<0.005). SLA class I and II expression on WT and GTKO pAECs was comparable. Human CD4+ and CD8+ T-cell proliferation was less against GTKO pAECs before (P<0.001) and after (P<0.01 and P<0.05, respectively) activation. Human and baboon PBMC proliferation was less against GTKO pAECs before (P<0.05) and after (P<0.01 and P<0.05, respectively) activation. Human PBMCs produced a comparable cytokine/chemokine response to WT and GTKO pAECs. However, there was less production of IFN-γ/TNF-α by CD4+ and IFN-γ/granzyme B/IP-10 by CD8+ T cells in response to GTKO pAECs.
  
  
  CONCLUSIONS
  The absence of Gal on pig cells is associated with reduced human T-cell proliferation (and possibly selected cytokine production). Adaptive primate T-cell responses are likely to be reduced in GTKO xenograft recipients.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Wilhite
authors.forename: Corin
authors.initials: C
authors.lastname: Ezzelarab
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Cassandra
authors.initials: C
authors.lastname: Long
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D004187:Disaccharides / Q000235:genetics / Q000276:immunology*; D004730:Endothelium, Vascular / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D010215:Papio; D013552:Swine; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D004187:Disaccharides; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; C438668:swine leukocyte antigen; C055075:galactosyl-(1-3)galactose; D000519:alpha-Galactosidase