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Quantitative tracking of T cell clones after haematopoietic stem cell transplantation.

Mamedov IZ, Britanova OV, Bolotin DA, Chkalina AV, Staroverov DB, Zvyagin IV, Kotlobay AA, Turchaninova MA, Fedorenko DA, Novik AA, Sharonov GV, Lukyanov S, Chudakov DM, Lebedev YB - EMBO Mol Med (2011)

Bottom Line: Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood.Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use it to perform the first detailed, quantitative tracking of T cell clones during 10 months after transplantation.We show that multiple clones survive the procedure, contribute to the immune response to activated infections, and form a new skewed and stable T cell receptor repertoire.

View Article: PubMed Central - PubMed

Affiliation: Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.

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Fate of the T cell clones that survived HSCTEach pie graph represents the total amount of TCR beta sequences obtained from a corresponding blood sample. Each slice represents the share of a clonal sequence or a group of clonal sequences, thus corresponding to abundance of specific T cell clones.Hyper-expanded clones (constituting >1% of all TCR beta sequences) before, 4 months after, and 10 months after transplantation are shown. Note that hyper-expanded clones constituted <3% of all T cells before and >20% after HSCT. Most of these clones were identified before HSCT at a low or medium level, but expanded dramatically after HSCT. CASSLSGGAGELFF was the only clone hyper-expanded in all three samples, while clone CASSVALGLNYEQYF was hyper-expanded before HSCT, but present at a relatively low level afterwards. The major CMV-specific clone CASSLAPGATNEKLFF-1 identified by MHC tetramer assay is shown in bold.Abundance of survived T cell clones within the overall T cell populations is shown. Those T cell clones, that survived HSCT initially, occupied only 12% of peripheral blood T cells before transplantation, but expanded to 40% of the population afterwards.
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fig01: Fate of the T cell clones that survived HSCTEach pie graph represents the total amount of TCR beta sequences obtained from a corresponding blood sample. Each slice represents the share of a clonal sequence or a group of clonal sequences, thus corresponding to abundance of specific T cell clones.Hyper-expanded clones (constituting >1% of all TCR beta sequences) before, 4 months after, and 10 months after transplantation are shown. Note that hyper-expanded clones constituted <3% of all T cells before and >20% after HSCT. Most of these clones were identified before HSCT at a low or medium level, but expanded dramatically after HSCT. CASSLSGGAGELFF was the only clone hyper-expanded in all three samples, while clone CASSVALGLNYEQYF was hyper-expanded before HSCT, but present at a relatively low level afterwards. The major CMV-specific clone CASSLAPGATNEKLFF-1 identified by MHC tetramer assay is shown in bold.Abundance of survived T cell clones within the overall T cell populations is shown. Those T cell clones, that survived HSCT initially, occupied only 12% of peripheral blood T cells before transplantation, but expanded to 40% of the population afterwards.

Mentions: HSCT decreased overall diversity of T cell clones (Supporting Information Fig 6), while the number of ‘hyper-expanded’ clones (comprising >1% of all TCR beta sequences) increased, leading to the propagation of specific TCR V beta gene families (Supporting Information Fig 7). The cumulative contribution of ‘hyper-expanded’ clones increased from 3% before to 26% after HSCT and remained at this high level for at least 10 months after HSCT (Fig 1A).


Quantitative tracking of T cell clones after haematopoietic stem cell transplantation.

Mamedov IZ, Britanova OV, Bolotin DA, Chkalina AV, Staroverov DB, Zvyagin IV, Kotlobay AA, Turchaninova MA, Fedorenko DA, Novik AA, Sharonov GV, Lukyanov S, Chudakov DM, Lebedev YB - EMBO Mol Med (2011)

Fate of the T cell clones that survived HSCTEach pie graph represents the total amount of TCR beta sequences obtained from a corresponding blood sample. Each slice represents the share of a clonal sequence or a group of clonal sequences, thus corresponding to abundance of specific T cell clones.Hyper-expanded clones (constituting >1% of all TCR beta sequences) before, 4 months after, and 10 months after transplantation are shown. Note that hyper-expanded clones constituted <3% of all T cells before and >20% after HSCT. Most of these clones were identified before HSCT at a low or medium level, but expanded dramatically after HSCT. CASSLSGGAGELFF was the only clone hyper-expanded in all three samples, while clone CASSVALGLNYEQYF was hyper-expanded before HSCT, but present at a relatively low level afterwards. The major CMV-specific clone CASSLAPGATNEKLFF-1 identified by MHC tetramer assay is shown in bold.Abundance of survived T cell clones within the overall T cell populations is shown. Those T cell clones, that survived HSCT initially, occupied only 12% of peripheral blood T cells before transplantation, but expanded to 40% of the population afterwards.
© Copyright Policy
Related In: Results  -  Collection

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fig01: Fate of the T cell clones that survived HSCTEach pie graph represents the total amount of TCR beta sequences obtained from a corresponding blood sample. Each slice represents the share of a clonal sequence or a group of clonal sequences, thus corresponding to abundance of specific T cell clones.Hyper-expanded clones (constituting >1% of all TCR beta sequences) before, 4 months after, and 10 months after transplantation are shown. Note that hyper-expanded clones constituted <3% of all T cells before and >20% after HSCT. Most of these clones were identified before HSCT at a low or medium level, but expanded dramatically after HSCT. CASSLSGGAGELFF was the only clone hyper-expanded in all three samples, while clone CASSVALGLNYEQYF was hyper-expanded before HSCT, but present at a relatively low level afterwards. The major CMV-specific clone CASSLAPGATNEKLFF-1 identified by MHC tetramer assay is shown in bold.Abundance of survived T cell clones within the overall T cell populations is shown. Those T cell clones, that survived HSCT initially, occupied only 12% of peripheral blood T cells before transplantation, but expanded to 40% of the population afterwards.
Mentions: HSCT decreased overall diversity of T cell clones (Supporting Information Fig 6), while the number of ‘hyper-expanded’ clones (comprising >1% of all TCR beta sequences) increased, leading to the propagation of specific TCR V beta gene families (Supporting Information Fig 7). The cumulative contribution of ‘hyper-expanded’ clones increased from 3% before to 26% after HSCT and remained at this high level for at least 10 months after HSCT (Fig 1A).

Bottom Line: Autologous haematopoietic stem cell transplantation is highly efficient for the treatment of systemic autoimmune diseases, but its consequences for the immune system remain poorly understood.Here, we describe an optimized RNA-based technology for unbiased amplification of T cell receptor beta-chain libraries and use it to perform the first detailed, quantitative tracking of T cell clones during 10 months after transplantation.We show that multiple clones survive the procedure, contribute to the immune response to activated infections, and form a new skewed and stable T cell receptor repertoire.

View Article: PubMed Central - PubMed

Affiliation: Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.

Show MeSH
Related in: MedlinePlus