Peripheral blood CD8αα+CD11c+MHC−II+CD3- cells attenuate autoimmune glomerulonephritis in rats
| Autor: | Cindy Zhou, Jean Wu, Colin Carlock, Julie M. Robertson, Yahuan Lou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Adoptive cell transfer Time Factors CD3 Complex Freund's Adjuvant Kidney Glomerulus Apoptosis Autoimmunity CD8-Positive T-Lymphocytes Rats Inbred WKY Blood Urea Nitrogen 0302 clinical medicine Glomerulonephritis Cells Cultured 0303 health sciences Adoptive Transfer 3. Good health Chemotaxis Leukocyte Nephrology Creatinine Female medicine.symptom CD3 CD8 Antigens CD11c Inflammation Biology Peripheral blood mononuclear cell Article 03 medical and health sciences Organ Culture Techniques medicine Animals 030304 developmental biology Histocompatibility Antigens Class II medicine.disease Molecular biology Coculture Techniques CD11c Antigen Disease Models Animal Freund's adjuvant Rats Inbred Lew Immunology biology.protein Peptides Biomarkers 030215 immunology |
| Zdroj: | Kidney international |
| ISSN: | 1523-1755 0085-2538 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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