Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment

Tamura, Jun’ichi; Kubota, Keiichi; Murakami, Hirokazu; Sawamura, Morio; Maekawa, Takafumi; Tamura, Tomohide; Saitoh, Takayuki; Kurabayshi, Hitoshi; Naruse, Takuji

doi:10.1046/j.1365-2249.1999.00870.x

Cited by 242 publications

(174 citation statements)

References 18 publications

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“…Vitamin A deficiency has also been shown to reduce the CD4 ϩ cell proportion in humans (39). A few in vivo studies showed a decrease in CD8 ϩ cell population with deficiencies in vitamin D (40), vitamin E (41), and vitamin B12 (42)(43)(44). Interestingly, vitamin B12 plays an important role in DNA metabolism and B12 deficiency can cause uracil misincorporation into DNA by the same mechanism as folate deficiency…”

Section: Discussionmentioning

confidence: 99%

Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes In Vitro

Courtemanche

Elson-Schwab

Mashiyama

et al. 2004

The Journal of Immunology

149

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Folate is required for one-carbon transfer reactions and the formation of purines and pyrimidines for DNA and RNA synthesis. Deficiency of folate can lead to many clinical abnormalities, including macrocytic anemia, cardiovascular diseases, birth defects, and carcinogenesis. The nucleotide imbalance due to folate deficiency causes cell cycle arrest in the S phase and uracil misincorporation into DNA, which may result in DNA double-strand breaks during repair. The role of folate in the immune system has not been fully characterized. We cultured PHA-activated human T lymphocytes in varying concentrations of folate, and measured proliferation, cell cycle, apoptosis, uracil misincorporation, and proportions of Th cells (CD4+) and cytotoxic T (CD8+) cells. Folate deficiency reduced proliferation of T lymphocytes, induced cell cycle arrest in the S phase, induced apoptosis, and increased the level of uracil in DNA. Folate deficiency also increased the CD4+ to CD8+ ratio due to a marked reduction of CD8+ cell proliferation. Folate or nucleoside repletion of folate-deficient cells rapidly restored T lymphocyte proliferation and normal cell cycle, reduced the DNA uracil content, and lowered the CD4+ to CD8+ ratio. These data suggest that folate status may affect the immune system by reducing the capacity of CD8+ cells to proliferate in response to activation.

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Section: Discussionmentioning

confidence: 99%

Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes In Vitro

Courtemanche

Elson-Schwab

Mashiyama

et al. 2004

The Journal of Immunology

149

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show abstract

“…A considerably suppressed NK cell activity was also noted in humans with B12 deiciency [35], as well as a decrease in the spleen NK activity was observed in rats on B12-deicient diet, although this efect was not statistically signiicant in the thymus or axillary nodes [36].…”

Section: Speciic Role Of Vitamin B12 In Immune System Functioningmentioning

confidence: 82%

“…In contrast, serum levels of immunoglobulins are not afected by vitamin B12 deiciency or supplementation [35].…”

Section: Speciic Role Of Vitamin B12 In Immune System Functioningmentioning

confidence: 98%

“…Methionine synthase, which uses methylcobalamin as a cofactor, is essential for the synthesis of purines B12 deiciency leads to a low number of lymphocytes and impairs the activity of NK cells (the most important for destroying cancer cells) [35]. More speciically, CD8+ cells are decreased in patients with B12 deiciency anemia when compared to control population.…”

Section: Speciic Role Of Vitamin B12 In Immune System Functioningmentioning

confidence: 99%

“…Intramuscular injections with B12 (under the form of methylcobalamin) in newly diagnosed B12-deicient patients completely restore the production of CD8+ T lymphocytes, the abnormally increased CD4/CD8 ratio, the CD3−CD16+ and CD16+CD57+ count (which possess strong NK cell activity), and hence the NK cells activity [35]. In contrast, serum levels of immunoglobulins are not afected by vitamin B12 deiciency or supplementation [35].…”

Section: Speciic Role Of Vitamin B12 In Immune System Functioningmentioning

confidence: 99%

See 2 more Smart Citations

Vitamin B12: Could It Be a Promising Immunotherapy?

Todorova¹,

Ermenlieva²,

Tsankova³

2017

Immunotherapy - Myths, Reality, Ideas, Future

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Vitamin B12 is a water-soluble vitamin and an important micronutrient with critical role in DNA, protein, and lipid synthesis. It is responsible for one-carbon metabolism and cell division of nervous and hematopoietic cells. Among its various functions, the role as immunomodulator in cellular immunity, especially in elevating the number of CD8+ cells and NK cells, atracts scientiic interest. Many alternative anticancer and anti-inlammatory treatments involve the use of B12 together with other vitamins and nutrients, but still the scientiic information is too obscure and insuicient. Controversial data link tumorigenesis with either increased or decreased B12 blood levels in diferent types of cancer. Dietary intake and additional supplement with the vitamin do not protect against cancer risk, but the dominant opinion is to integrate B12 as part of rational and healthy nutrition to ensure proper function of the immune system. This chapter will review in brief the most important facts for vitamin B12 functions and properties. We will try also to present in concise way the human immune system and the exact role of B12 in immune activity with emphasis on the questionable participation of vitamin B12 in the process of carcinogenesis and its signiicance as anticancer immunotherapy.Keywords: vitamin B12, immunonutrition, immunomodulation, immunotherapy, tumorigenesis, cancer, inlammation IntroductionCancer is the inal outcome of uncontrolled overgrowth of normal cells. Cancer cells remain insensitive to antiproliferative signals and apoptosis. As a result, they replicate, proliferate, and invade ininitely and aggressively. Although the genetic events are thought to be the most important in the process of carcinogenesis, other factors can facilitate abnormal cell development. For many years, inlammation and anti-inlammatory response were widely associated with malignancy [1, 2] and recognized as major elements that trigger carcinogenesis.© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Extended inlammation, especially in chronic infections, predisposes to cancer, but still the mechanism(s) involved is (are) not deinitely known. Usually all inlammatory processes are followed rapidly by anti-inlammatory defense response-excessive production of proinlammatory signals (mediators) and reactive oxygen and nitrogen species. The pro-inlammatory mediators (cytokines, chemokines, and eicosanoids) may stimulate proliferation of both untransformed and tumor cells [2]. The reactive oxygen and nitrogen species lead to oxidative stress and damage of macromolecules, especially DNA to increase the risk of genetic mutations and tumorigenesis [3].A continuously increasing number of microelements, vitamins, and mineral salts are reported to modulate the immune response and counter the inlamm...

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Age‐Related Gastrointestinal Conditions and Considerations for Nutrition

Cox¹

2017

Treatment and Care of the Geriatric Veterinary Patient

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Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment

Cited by 242 publications

References 18 publications

Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes In Vitro

Folate Deficiency Inhibits the Proliferation of Primary Human CD8+ T Lymphocytes In Vitro

Vitamin B12: Could It Be a Promising Immunotherapy?

Age‐Related Gastrointestinal Conditions and Considerations for Nutrition

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