Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo

Mauro Di Ianni, Lorenzo Moretti, Adelmo Terenzi, Federico Bazzucchi, Beatrice Del Papa, Moira Bazzucchi, Raffaella Ciurnelli, Alessandro Lucchesi, Paolo Sportoletti, Emanuela Rosati, Pier Francesco Marconi, Franca Falzetti, Antonio Tabilio

Research output: Contribution to journalArticle

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Abstract

Background aims: The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Methods: Freshly isolated CD3+ T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Results: Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index > 30% was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. Conclusions: This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

Original languageEnglish
Pages (from-to)86-96
Number of pages11
JournalCytotherapy
Volume11
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

B-Cell Leukemia
B-Cell Chronic Lymphocytic Leukemia
T-Lymphocytes
B-Lymphocytes
In Vitro Techniques
Muromonab-CD3
Inbred NOD Mouse
SCID Mice
K562 Cells
Gene Expression Profiling
Tumor Burden
Cytoskeleton
Transcriptome
Cell Differentiation
Immune System
Blood Cells
Cell Count

Keywords

  • Autologous anti-tumoral activity
  • Chronic lymphatic leukemia
  • Gene expression profiling
  • NOD/SCID mice
  • OKT3 activation
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

Cite this

Di Ianni, M., Moretti, L., Terenzi, A., Bazzucchi, F., Del Papa, B., Bazzucchi, M., ... Tabilio, A. (2009). Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo. Cytotherapy, 11(1), 86-96. https://doi.org/10.1080/14653240802666035

Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo. / Di Ianni, Mauro; Moretti, Lorenzo; Terenzi, Adelmo; Bazzucchi, Federico; Del Papa, Beatrice; Bazzucchi, Moira; Ciurnelli, Raffaella; Lucchesi, Alessandro; Sportoletti, Paolo; Rosati, Emanuela; Marconi, Pier Francesco; Falzetti, Franca; Tabilio, Antonio.

In: Cytotherapy, Vol. 11, No. 1, 2009, p. 86-96.

Research output: Contribution to journalArticle

Di Ianni, M, Moretti, L, Terenzi, A, Bazzucchi, F, Del Papa, B, Bazzucchi, M, Ciurnelli, R, Lucchesi, A, Sportoletti, P, Rosati, E, Marconi, PF, Falzetti, F & Tabilio, A 2009, 'Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo', Cytotherapy, vol. 11, no. 1, pp. 86-96. https://doi.org/10.1080/14653240802666035
Di Ianni, Mauro ; Moretti, Lorenzo ; Terenzi, Adelmo ; Bazzucchi, Federico ; Del Papa, Beatrice ; Bazzucchi, Moira ; Ciurnelli, Raffaella ; Lucchesi, Alessandro ; Sportoletti, Paolo ; Rosati, Emanuela ; Marconi, Pier Francesco ; Falzetti, Franca ; Tabilio, Antonio. / Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo. In: Cytotherapy. 2009 ; Vol. 11, No. 1. pp. 86-96.
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abstract = "Background aims: The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Methods: Freshly isolated CD3+ T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Results: Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index > 30{\%} was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. Conclusions: This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.",
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T1 - Activated autologous T cells exert an anti-B-cell chronic lymphatic leukemia effect in vitro and in vivo

AU - Di Ianni, Mauro

AU - Moretti, Lorenzo

AU - Terenzi, Adelmo

AU - Bazzucchi, Federico

AU - Del Papa, Beatrice

AU - Bazzucchi, Moira

AU - Ciurnelli, Raffaella

AU - Lucchesi, Alessandro

AU - Sportoletti, Paolo

AU - Rosati, Emanuela

AU - Marconi, Pier Francesco

AU - Falzetti, Franca

AU - Tabilio, Antonio

PY - 2009

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N2 - Background aims: The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Methods: Freshly isolated CD3+ T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Results: Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index > 30% was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. Conclusions: This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

AB - Background aims: The impact of chronic lymphatic leukemia (CLL) tumor burden on the autologous immune system has already been demonstrated. This study attempted to elucidate the molecular mechanisms underlying T-cell immunologic deficiencies in CLL. Methods: Freshly isolated CD3+ T cells from patients with a diagnosis of CLL and healthy donors were analyzed by gene expression profiling. Activated T cells from 20 patients with CLL were tested in vitro for cytotoxicity against mutated and unmutated autologous B cells and DAUDI, K562 and P815 cell lines. To investigate T-cell mediated cytotoxicity in vivo, we co-transplanted OKT3-activated T lymphocytes and autologous B-cell CLL (B-CLL) cells into NOD/SCID mice. Results: Gene expression profiles of peripheral blood T cells from B-CLL patients showed 25 down-regulated, and 31 up-regulated, genes that were mainly involved in cell differentiation, proliferation, survival, apoptosis, cytoskeleton formation, vesicle trafficking and T-cell activation. After culture, the T-cell count remained unchanged, CD8 cells expanded more than CD4 and a cytotoxicity index > 30% was present in 5/20 patients. Cytotoxicity against B autologous leukemic cells did not correlate with B-cell mutational status. Only activated T cells exerting cytotoxicity against autologous leukemic B cells prevented CLL in a human-mouse chimera. Conclusions: This study indicates that patients with CLL are affected by a partial immunologic defect that might be somewhat susceptible to repair. This study identifies the molecular pathways underlying T-cell deficiencies in CLL and shows that cytotoxic T-cell functions against autologous B-CLL can be rebuilt at least in part in vitro and in vivo.

KW - Autologous anti-tumoral activity

KW - Chronic lymphatic leukemia

KW - Gene expression profiling

KW - NOD/SCID mice

KW - OKT3 activation

KW - T lymphocytes

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