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

K M Wiers; Y Lozano; K A Messingham; R J Metz; M R Young

doi:10.1007/s002620050361

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

Journal article

Peer reviewed

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

K M Wiers, Y Lozano, K A Messingham, R J Metz and M R Young

Cancer immunology, immunotherapy : CII, Vol.44(2), pp.97-102

04/1997

DOI: 10.1007/s002620050361

PMCID: PMC11037722

PMID: 9177471

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Abstract

The sterol 1alpha,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 gamma 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.

Spleen - immunology

Carcinoma, Lewis Lung - enzymology

Enzyme-Linked Immunosorbent Assay

Mice, Inbred C57BL

Phosphoprotein Phosphatases - metabolism

Carcinoma, Lewis Lung - immunology

Interferon-gamma - drug effects

Interferon-gamma - metabolism

Lymph Nodes - immunology

Cell Division - drug effects

Dose-Response Relationship, Drug

Lymph Nodes - enzymology

Lymphocyte Activation - immunology

Animals

Spleen - enzymology

T-Lymphocytes - metabolism

Lymphocyte Activation - drug effects

Calcitriol - pharmacology

CD3 Complex - immunology

Receptors, Antigen, T-Cell - immunology

T-Lymphocytes - immunology

Mice

Tumor Cells, Cultured

Protein Phosphatase 2

Details

Title: Subtitle: 1α ,25-Dihydroxyvitamin D3 activates T cells of tumor bearers through protein phosphatase 2A
Creators: K M Wiers - Research Service, Hines VA Hospital, IL 60141, USA
Y Lozano
K A Messingham
R J Metz
M R Young
Resource Type: Journal article
Publication Details: Cancer immunology, immunotherapy : CII, Vol.44(2), pp.97-102
DOI: 10.1007/s002620050361
PMID: 9177471
PMCID: PMC11037722
NLM abbreviation: Cancer Immunol Immunother
ISSN: 0340-7004
eISSN: 1432-0851
Publisher: Germany
Grant note: CA-48080 / NCI NIH HHS CA-45080 / NCI NIH HHS
Language: English
Date published: 04/1997
Academic Unit: Dermatology
Record Identifier: 9984025405302771

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