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T-cell responses af...
T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis
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- Burman, Joachim (author)
- Uppsala universitet,Neurologi,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Fransson, Moa (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Tötterman, Thomas H. (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Fagius, Jan (author)
- Uppsala universitet,Neurologi
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- Mangsbo, Sara M. (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Loskog, Angelica S. I. (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2013-09-12
- 2013
- English.
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In: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 140:2, s. 211-219
- Related links:
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https://www.ncbi.nlm...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Autologous haematopoietic stem cell transplantation (HSCT) for relapsing-remitting multiple sclerosis is a potentially curative treatment, which can give rise to long-term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD4(+) T-cell populations between HSCT-treated patients (n = 12) and healthy controls (n = 9). Phenotyping of memory T cells, regulatory T (Treg) cells and T helper type 1 (Th1) and type 17 (Th17) cells was performed. Further, T-cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab (n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T-cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT-treated patients had similar levels of Treg cells and of Th1 and Th17 cells as healthy subjects, whereas natalizumab-treated patients had lower frequencies of Treg cells, and higher frequencies of Th1 and Th17 cells. Cells from HSCT-treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor-beta(1) than natalizumab-treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab-treated patients cultured with those peptides produced more interleukin-17 (IL-17), IL-1 and IL-10, indicating a Th17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T-cell clones as well as development of tolerance after HSCT. These results parallel the long-term disease remission seen after HSCT.
Keyword
- haematopoietic stem cell transplantation
- multiple sclerosis
- natalizumab
- neuroimmunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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