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CLL and Normal B and T Cells

Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia

Leukemia volume 19, pages 1788–1793 (2005)Cite this article

Abstract

Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Since CD152 (CTLA-4) plays a critical role in downregulating T-cell responses, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from treatment-naïve patients with CLL. CD4+ and CD8+ T cells from these patients demonstrated significantly increased sCD152 and cCD152 compared to normal donors. Furthermore, these patients had an increased proportion of the regulatory CD4+/CD25+/CD152+ subset that correlated with advanced Rai stage, unfavorable cytogenetics and low serum IgG and IgA levels. The expression of sCD152 by T cells also correlated with ZAP-70 expression by CLL B cells. The proportion of CD4+/CD25+ cells was also correlated with unmutated immunoglobulin heavy chain variable gene status. Blockade of CD152 with monoclonal antibody (mAb) in proliferation assays was associated with potent T-cell proliferation in response to autologous and allogeneic CD40-activated CLL B cells. In summary, T cells from patients with CLL may be primed for anergy by expressing increased amounts of CD152; anti-CD152 mAb may represent a therapeutic opportunity to enhance an immune response against autologous leukemia cells.

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Acknowledgements

This work was supported in part by P50 CA100632-01 and 2PO1 CA81534-02 and Collegio Ghislieri, Centro per la Comunicazione e la Ricerca, Pavia, Italy. We thank Dr Simona M Pino for technical assistance in MLR analysis.

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Authors and Affiliations

  1. Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX, USA

    M Motta, B J Shelvin, S Lerner, M J Keating & W G Wierda

  2. CLL Research Consortium, San Diego, CA, USA

    L Rassenti, T J Kipps, M J Keating & W G Wierda

Authors
  1. M Motta
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  2. L Rassenti
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  3. B J Shelvin
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  4. S Lerner
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  5. T J Kipps
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  6. M J Keating
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  7. W G Wierda
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Correspondence to W G Wierda.

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Motta, M., Rassenti, L., Shelvin, B. et al. Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia. Leukemia 19, 1788–1793 (2005). https://doi.org/10.1038/sj.leu.2403907

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