Interactions of 1 alpha,25-dihydroxyvitamin D3 with IL-12 and IL-4 on cytokine expression of human T lymphocytes.
BACKGROUND
1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25[OH](2)D(3)) exerts its effects on the immune system, particularly through suppression of T helper/cytotoxic cell 1 (T(H)/T(C)1)-mediated reactions, although direct actions of 1 alpha,25(OH)(2)D(3) on human T lymphocytes have not yet been studied in detail.


OBJECTIVE
We evaluated the effect of 1 alpha,25(OH)(2)D(3) on basal and cytokine-driven T-cell functions at the single-cell level.


METHODS
We used 4-color flow cytometry for simultaneous detection of intracellular cytokines in CD4(+) and CD8(+) human PBMCs that had been cultured in the presence of 1 alpha,25(OH)(2)D(3) singly or in combination with either IL-12 or IL-4. According to the exploratory nature of these investigations, the Bonferroni correction was not applied for data analysis and presentation.


RESULTS
1 alpha,25(OH)(2)D(3) had little effect on T(H)/T(C)1 cytokines but significantly inhibited IL-12-induced IFN-gamma production. Constitutive synthesis of T(H)/T(C)2-related cytokines was also only modestly affected by 1 alpha,25(OH)(2)D(3) alone. When T(H)/T(C)2 differentiation was induced by IL-4, 1 alpha,25(OH)(2)D(3) significantly expanded the percentages of IL-4(+) and IL-13(+) cells. However, the predominant effect of 1 alpha,25(OH)(2)D(3) on T lymphocytes, particularly in the presence of IL-4, was the induction of separate CD4(+) and CD8(+) subpopulations with almost exclusive expression of IL-6. This might be an important facet of the immunomodulatory action of 1 alpha,25(OH)(2)D(3) because IL-6 might act in parallel with 1 alpha,25(OH)(2)D(3) in modulation of T(H)/T(C) effector cell functions.


CONCLUSIONS
Our data imply that the specific actions of 1 alpha,25(OH)(2)D(3) on cytokine-stimulated T-cell functions could play a role in the prevention of T(H)/T(C)1-related autoimmune diseases but also predispose toward T(H)/T(C)2-mediated allergic reactions.
Thien
Ralf
R
Department of Pathophysiology, Medical University of Vienna, Austria.
Baier
Karin
K
Pietschmann
Peter
P
Peterlik
Meinrad
M
Willheim
Martin
M
D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D016207:Cytokines; D018793:Interleukin-13; D015850:Interleukin-6; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma