title: Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats.
abstract: In an anti-glomerular basement membrane (GBM) glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα+CD11c+MHC-II+CD3- (GIL CD8αα+ cells) were responsible for recovery through induction of T-cell apoptosis. Now, we identified peripheral blood CD8αα+CD11c+MHC-II+CD3- cells (PBMC CD8αα+CD3- cells), which shared 9 markers with GIL CD8αα+ cells. Upon incubation, PBMC CD8αα+CD3- cells displayed a morphology resembling that of dendritic cells. Similar to GIL CD8αα+ cells, PBMC CD8αα+CD3- cells were capable of inducing T-cell apoptosis in vitro. Hence, PBMC CD8αα+CD3- cells were likely the precursor of GIL CD8αα+ cells. We next tested their potential in vivo function. PBMC CD8αα+CD3- cells were able to infiltrate inflamed but not normal glomeruli. Isolated PBMC CD8αα+CD3- cells of Lewis rats were transferred into GN-prone Wistar-Kyoto rats at early inflammatory stage (days 17-25). When examined at day 45, both histopathology and blood urea nitrogen/serum creatinine level showed significantly attenuated GN in 80% of cell recipient Wistar-Kyoto rats. Separate experiments verified infiltration of transferred Lewis PBMC CD8αα+CD3- into the glomeruli, accompanied with apoptotic CD4+ T cells in the glomeruli of the recipient Wistar-Kyoto rats. Thus, PBMC CD8αα+CD3- cells of Lewis rats were able to terminate ongoing autoimmune inflammation in the glomeruli.
authors.affiliation: Department of Diagnostic and Biomedical Sciences, SD, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Diagnostic and Biomedical Sciences, SD, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Diagnostic and Biomedical Sciences, SD, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Department of Diagnostic and Biomedical Sciences, SD, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Carlock
authors.affiliation: Department of Diagnostic and Biomedical Sciences, SD, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Ya-Huan
authors.initials: YH
authors.lastname: Lou
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D039521:CD11c Antigen / Q000097:blood*; D017252:CD3 Complex / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016827:CD8 Antigens / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D003404:Creatinine / Q000097:blood; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D005921:Glomerulonephritis / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000097:blood*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D009924:Organ Culture Techniques; D010455:Peptides; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D013997:Time Factors
chemical_list: D015415:Biomarkers; D039521:CD11c Antigen; D017252:CD3 Complex; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D005620:Freund's Adjuvant; D003404:Creatinine