1α ,25-Dihydroxyvitamin D3 activates T cells of tumor bearers through protein phosphatase 2A (original) (raw)

Abstract

The sterol 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit T cell activation as well as restore the functional competence of suppressed T cells. The present studies determined whether 1,25(OH)2D3 had a differential effect on the activation of normal T cells or of suppressed T cells from mice bearing Lewis lung carcinoma tumors. Normal spleen cell proliferation in response to immobilized anti-CD3 was unaffected by the lower doses of 0.1 – 10 nM 1,25(OH)2D3, and was inhibited by the higher dose of 100 nM 1,25(OH)2D3. In contrast, 1,25(OH)2D3 increased proliferation and interferon γ secretion by T cells of tumor bearers in response to stimulation through T cell receptor/CD3. Assessment of mechanisms associated with the 1,25(OH)2D3 stimulation of tumor-bearer T cells implicated protein phosphatase 2A (PP-2A). First, PP-2A activity of spleen cells from tumor bearers was reduced compared to that of normal spleen cells but was increased by 1,25(OH)2D3. Second, 1,25(OH)2D3 stimulation of tumor-bearer T cell proliferation was dependent on this PP-2A activity as it was blocked by doses of okadaic acid that selectively inhibit PP-2A. These results suggest that 1,25(OH)2D3 preferentially enhances the responsiveness of immunosuppressed T cells from tumor bearers to TCR/CD3 stimulation by restoring PP-2A activity.

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Authors and Affiliations

  1. Research Service (151-Z2) Hines VA Hospital, Hines, IL 60141, USAFax: (708) 216 – 2319 e-mail: ryoung@bsd.meddean.luc.edu, , , , , , US
    Kristina M. Wiers, Yvonne Lozano & M. R. I. Young
  2. Department of Pathology, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA, , , , , , US
    Raymond J. Metz
  3. Department of Cell Biology, Neuroscience and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA, , , , , , US
    K. A. N. Messignham

Authors

  1. Kristina M. Wiers
  2. Yvonne Lozano
  3. K. A. N. Messignham
  4. Raymond J. Metz
  5. M. R. I. Young

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Received: 7 November 1996 / Accepted: 2 January 1997

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Wiers, K., Lozano, Y., Messignham, K. et al. 1α ,25-Dihydroxyvitamin D3 activates T cells of tumor bearers through protein phosphatase 2A.Cancer Immunol Immunother 44, 97–102 (1997). https://doi.org/10.1007/s002620050361

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