Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats

Kidney Int. 2014 May;85(5):1078-90. doi: 10.1038/ki.2013.456. Epub 2013 Nov 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Apoptosis
  • Autoimmunity*
  • Biomarkers / blood
  • Blood Urea Nitrogen
  • CD11c Antigen / blood*
  • CD3 Complex / blood*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8 Antigens / blood*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / transplantation*
  • Cells, Cultured
  • Chemotaxis, Leukocyte
  • Coculture Techniques
  • Creatinine / blood
  • Cytotoxicity, Immunologic
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant
  • Glomerulonephritis / blood
  • Glomerulonephritis / chemically induced
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Glomerulonephritis / prevention & control*
  • Histocompatibility Antigens Class II / blood*
  • Kidney Glomerulus / immunology*
  • Kidney Glomerulus / pathology
  • Organ Culture Techniques
  • Peptides
  • Rats, Inbred Lew
  • Rats, Inbred WKY
  • Time Factors


  • Biomarkers
  • CD11c Antigen
  • CD3 Complex
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Histocompatibility Antigens Class II
  • Peptides
  • Freund's Adjuvant
  • Creatinine