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Poor induction of interleukin-2 receptor expression on CD8bright+ cells in whole blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb

  • Original Articles
  • Whole Blood Assay, IL-2R Expression, CD3 Stimulation, IFNγ Immunotherapy
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

To induce better stimulation of T cells during recombinant interleukin-2 (rIL-2) therapy of renal cell carcinoma patients, pretreatment with low-dose CD3 monoclonal antibody (mAb) has been proposed. However, in our clinic, such a treatment did not induce additional activation of T cells. To investigate this we performed whole blood cell cultures with rIL-2 or CD3 mAb as a stimulant. Cultures using isolated blood mononuclear cells were used as a control. When stimulated by the addition of rIL-2, the lymphocyte composition and activation of whole blood cultures did not differ from those of mononuclear cell (MNC) cultures. However, when stimulation was performed with CD3 mAb, CD8bright+ cells in whole blood cultures were not or only minimally induced to express CD25 or IL-2 receptor β (IL-2R\). This is in contrast to the situation found in MNC cultures where all CD8bright+ cells expressed CD25 or IL-2Rß to a high extent at the end of culture. When rIL-2 or recombinant interferon γ (rIFNγ) was added to whole blood cultures together with CD3 mAb, significantly more CD8bright+ cells were induced to express CD25 or IL-2Rß. These results suggest that whole blood cultures represent the in vivo situation better than MNC cultures. In addition, the results suggest that, also in vivo, administration of low-dose CD3 mAb alone might not be sufficient to induce IL-2R expression on CD8bright+ cells, and would therefore not induce additional specific T cell activation in rIL-2-based immunotherapy. The presented results suggest that in vivosimultaneous administration of rIFNγ or rIL-2 with low-dose CD3 mAb might induce better stimulation of CD8+ T cells than CD3 mAb only.

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Authors and Affiliations

  1. Department of Clinical Immunology, University Hospital Groningen, Internal Medicine, 9713 EZ, Groningen, The Netherlands

    Richard A. J. Janssen, Agnes A. Heijn, T. Hauw The & Lou de Leij

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  1. Richard A. J. Janssen
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  2. Agnes A. Heijn
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  3. T. Hauw The
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  4. Lou de Leij
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Janssen, R.A.J., Heijn, A.A., Hauw The, T. et al. Poor induction of interleukin-2 receptor expression on CD8bright+ cells in whole blood cell cultures with CD3 mAb. Implications for immunotherapy with CD3 mAb. Cancer Immunol Immunother 38, 53–60 (1994). https://doi.org/10.1007/BF01517170

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  • DOI: https://doi.org/10.1007/BF01517170

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