title: Human T cells upregulate CD69 after coculture with xenogeneic genetically-modified pig mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSC) obtained from α1,3-galactosyltransferase gene knock-out pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46 pMSC) suppress in vitro human anti-pig cellular responses as efficiently as allogeneic human MSC. We investigated the immunoregulatory effects of GTKO/CD46 pMSC on human CD4(+) and CD8(+) T cell proliferation in response to pig aortic endothelial cells (pAEC). pMSC efficiently suppressed T cell proliferation, which was associated with downregulation of granzyme B expression. No induction of CD4(+)CD25(+)Foxp3(hi) regulatory T cells or T cell apoptosis was documented. In correlation with T cell proliferation, CD25 expression was upregulated on T cells in response to pAEC but not to pMSC. In contrast, CD69 expression was upregulated on T cells in response to both pMSC and pAEC, which was associated with a significant increase in the phosphorylation of STAT5. GTKO/CD46 pMSC possibly regulate human T cell responses through modulation of CD69 expression and STAT5 signaling.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Transplantation Surgery, Tianjin First Center Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Oleg
authors.initials: O
authors.lastname: Andreyev
authors.forename: Man
authors.initials: M
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Marco
authors.forename: Hayato
authors.initials: H
authors.lastname: Iwase
authors.forename: Cassandra
authors.initials: C
authors.lastname: Long
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Shen
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Ezzelarab
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005700:Galactosyltransferases / Q000235:genetics; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D039661:Integrin beta3 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013552:Swine; D014183:Transplantation, Heterologous; D015854:Up-Regulation; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051858:Forkhead Transcription Factors; D005700:Galactosyltransferases; D053804:Granzymes; D039661:Integrin beta3; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D051916:Membrane Cofactor Protein; D050799:STAT5 Transcription Factor; D000099192:CD69 Antigens; C418974:FOXP3 protein, human; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase
keywords: CD69; GTKO/CD46; GTKO/hCD46; Gal; LAG-3; Mesenchymal stem cells; PBMC; Pig; STAT5; T cells; Xenotransplantation; galactose-α1,3-galactose; lymphocyte activation gene-3; pAEC; pMSC; pSTAT5; peripheral blood mononuclear cells; phosphorylated signal transducer and activator of transcription 5; pig aortic endothelial cells; pig mesenchymal stromal cells; α1,3-galactosyltransferase gene-knockout/human CD46
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