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

In an anti-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 w...

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Autores principales: Wu, Jean, Zhou, Cindy, Robertson, Julie, Carlock, Colin, Lou, Yahuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008668/
https://www.ncbi.nlm.nih.gov/pubmed/24257693
http://dx.doi.org/10.1038/ki.2013.456
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author Wu, Jean
Zhou, Cindy
Robertson, Julie
Carlock, Colin
Lou, Yahuan
author_facet Wu, Jean
Zhou, Cindy
Robertson, Julie
Carlock, Colin
Lou, Yahuan
author_sort Wu, Jean
collection PubMed
description In an anti-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 (day 17–25). When examined at day 45, both histopathology and BUN/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.
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spelling pubmed-40086682014-11-01 Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats Wu, Jean Zhou, Cindy Robertson, Julie Carlock, Colin Lou, Yahuan Kidney Int Article In an anti-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 (day 17–25). When examined at day 45, both histopathology and BUN/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. 2013-11-20 2014-05 /pmc/articles/PMC4008668/ /pubmed/24257693 http://dx.doi.org/10.1038/ki.2013.456 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wu, Jean
Zhou, Cindy
Robertson, Julie
Carlock, Colin
Lou, Yahuan
Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title_full Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title_fullStr Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title_full_unstemmed Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title_short Peripheral blood CD8αα(+)CD11c(+)MHC(−)II(+)CD3- cells attenuate autoimmune glomerulonephritis in rats
title_sort peripheral blood cd8αα(+)cd11c(+)mhc(−)ii(+)cd3- cells attenuate autoimmune glomerulonephritis in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008668/
https://www.ncbi.nlm.nih.gov/pubmed/24257693
http://dx.doi.org/10.1038/ki.2013.456
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