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Supplement: Immunonutrition: Enhancing Tumoricidal Cell Activity

Is the Increase in T Cell Priming by Dietary Alkylamines Sufficient to Prevent Cancer? What Other Components of the Diet Prime T Cells?¹

Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

²To whom correspondence should be addressed. E-mail: jbukowski{at}rics.bwh.harvard.edu.

KEY WORDS: • T cells • alkylamines • tea • L-theanine

T cells comprise 2–5% of T cells in human peripheral blood. They are expanded in the peripheral blood of patients with a variety of bacterial, viral, and parasitic illnesses to represent 50–60% of peripheral blood T cells. They are efficient secretors of interferon (IFN)³ and TNF-, and they mediate cytotoxicity against tumor cells and cells infected with microbes. They recognize, in a T cell receptor-dependent manner, nonpeptide alkyl phosphate and alkylamine antigens. This reactivity is not major histocompatibility complex- or cluster designation 1-restricted, does require cell-to-cell contact, and thus may require an antigen-presenting element.

We have shown that exposure of (PBMC) or cloned T cells to alkylamines results specifically in T cell expansion, Th1 cytokine secretion, cytotoxic activity, and an increase in the efficacy of antimicrobial protection (1–4). The largest known dietary source of alkylamine is L-theanine, an amino acid that is unique to tea, and occurs in 2 mM concentrations in tea beverage. Catabolism of L-theanine produces ethylamine, a T cell antigen. Our subsequent studies showed that subjects who started drinking 5–6 cups of tea, but not coffee, per day had a 5- to 15-fold greater IFN- response when their PBMC were exposed to bacteria (4). Thus, tea drinking did not by itself cause in vivo expansion or cytokine secretion, but it primed T cells to act more effectively in the face of a microbial challenge. This is important, because T cells have been shown to be a critical first line of defense against a wide variety of bacteria, viruses, parasites, fungi, and tumors. Equally important is the lack of side effects or perturbations to the immune system in the unchallenged state. These data suggest that many people have T cell function that is suboptimal to protect against microbes and tumors. We view tea and its L-theanine component as the first discovered essential vegetable nutrients for a healthy immune system, much the same way vitamins A and C are essential for healthy eyes and gums. The epigallocatechin-3-gallate (EGCG) and other antioxidants in tea are hypothesized to damp down the inflammatory and free-radical mediated damage during an immune response, perhaps leading to decreased immunopathology and recovery times. Thus, tea could be an effective countermeasure to infection risk and immune suppression in normal, healthy subjects.

Previous research on the health effects of tea has suggested that tea has anticancer effects, promotes increased oral health, retards autoimmune disease, and has positive cardiovascular effects. The best results come from drinking at least 10 cups per day, which is commonplace in some Asian societies but uncommon in the United States and even Europe. However, most studies to date have been observational. Interventional placebo-controlled trials measuring health outcomes in both healthy and at-risk populations using a capsule containing L-theanine and EGCG equivalent to 10–14 cups of tea per day are currently being planned.

FOOTNOTES

¹ Published in a supplement to The Journal of Nutrition. Presented during a workshop entitled: "Immunonutrition: Enhancing Tumoricidal Cell Activity," held in Bethesda, MD, March 23, 2005. This workshop was sponsored by the Division of Cancer Prevention, NCI, NIH, DHHS. Guest editors for the supplement publication were Susan S. Percival, John A. Milner, and Christopher A. Jolly. Guest Editor Disclosure: Susan S. Percival: no relationships to disclose; John A. Milner: no relationships to disclose; Christopher A. Jolly: received reimbursement for travel expenses from NCI.

³ Abbreviations used: EGCG, epigallocatechin-3-gallate; IFN, interferon; PBMC, peripheral blood mononuclear cells.

LITERATURE CITED

1. Bukowski JF, Morita CT, Brenner MB. Human gamma delta T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity. 1999;11:57-65.[Medline]

2. Bukowski JF, Morita CT, Brenner MB. Recognition and destruction of virus-infected cells by human CTL. J Immunol. 1994;153:5133-5140.[Abstract]

3. Wang L, Kamath A, Das H, Li L, Bukowski J. Antibacterial effect of human Vg2Vd2 T cells in vivo. J Clin Invest. 2001;108:1349-1357.[Medline]

4. Kamath AB, Wang L, Das H, Li L, Reinhold VN, Bukowski JF. Antigens in tea-beverage prime human V2V2 T cells in vitro and in vivo for memory and nonmemory antibacterial cytokine responses. Proc Natl Acad Sci U S A. 2003;100:6009-6014.[Abstract/Free Full Text]

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