Abstract

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e., resveratrol (Res), epigallocatechin-3-gallate (EGCG)) on the adaptive immune response, as well as their synergistic or antagonistic interactions. Freshly isolated T lymphocytes from healthy individuals were activated with anti-CD3/CD28 antibodies for 4–5 days in the presence of bioactives and were analyzed by cytofluorometry. Interleukins, cytokines, and chemokines were measured by multiple ELISA. Gene expression was measured by quantitative RT-PCR. Res and EGCG increased CD4 surface intensity. EGCG led to an increased proportion of CD8+ lymphocytes. Anti-CD3/CD28 activation induced exuberant secretion of interleukins and cytokines by T lymphocyte subsets. VD strongly enhanced Th2 cytokines (e.g., IL-5, IL-13), whereas Res and EGCG favored secretion of Th1 cytokines (e.g., IL-2, INF-γ). Res and VD mutually influenced cytokine production, but VD dominated the cytokine secretion pattern. The substances changed gene expression of interleukins and cytokines in a similar way as they did secretion. Collectively, VD strongly modulated cytokine and interleukin production and favored Th2 functions. Resveratrol and EGCG promoted the Th1 response. VA and VE had only a marginal effect, but they altered both Th1 and Th2 response. In vivo, bioactives might therefore interact with vitamins and support the outcome and extent of the adaptive immune response.

Highlights

  • The interactions between cell populations such as T and B lymphocytes orchestrate the highly complex pattern of the immune response to pathogens

  • We evaluated the relative contribution of vitamins and bioactives to interleukin and cytokine production in activated human T lymphocytes, and we investigated their effects on activated human T lymphocyte function

  • Effects of Res, epigallocatechin 3-gallate (EGCG), and Vitamins on the Phenotype of In Vitro Activated T Cells We investigated whether anti-CD3/CD28 activated T lymphocytes had an altered phenotype when they were cultured in the presence of substances

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Summary

Introduction

The interactions between cell populations such as T and B lymphocytes orchestrate the highly complex pattern of the immune response to pathogens. T lymphocytes differentiate into two main distinct subsets of T effector cells, T helper type 1 (Th1) and T helper type 2 (Th2) cells (reviewed in: [1]). Th1 cells secrete IL-2, IFN-γ, and TNF-α and are important for the development of delayed type hypersensitivity reactions and protective responses to intracellular pathogens [2]. Th2 lymphocytes express and secrete IL-4, IL-5, and/or IL-13 and are essential for the development of humoral and allergic reactions. The cytokine milieu of the local microenvironment is a major determinant of the direction of Th cell differentiation. Recent evidence suggests an important role for cytokines such as IL-1α, IL-1β, IL-15, and IL-18 in stimulating Th1 responses [2] and IL-10 and IL-13 in stimulating Th2 responses [3]

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