Effects of breastfeeding on immune response of CD4+T lymphocytes in infants

doi:10.11852/zgetbjzz2023-0633

Abstract

Abstract: Objective To explore the effects of breastfeeding on the immune response of CD4⁺T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. Methods A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children's Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4⁺ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. Results Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). Conclusions Breastfeeding has a regulatory effect on the immune response of infant CD4⁺ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.

Key words: breastfeeding, acquired immunity, CD4⁺T cell, helper T cell, regulatory T cell

摘要： 目的探索母乳喂养对婴儿在非炎症状态下的CD4⁺T淋巴细胞免疫反应的影响,并分析母乳整体成分的免疫调节意义,为提倡母乳喂养提供理论支持。方法本研究采用回顾性队列研究,按照入组标准选取2022年1—9月在南通大学附属常州儿童医院儿保科进行体检的6月龄婴儿为研究对象。根据喂养方式分为母乳喂养组(33例)和配方奶喂养组(27例)。采用流式细胞术检测外周血的CD4⁺T淋巴细胞,包括辅助性T淋巴细胞(Th)1、Th2、Th17和调节性T淋巴细胞(Treg)的百分比,以及相关细胞因子白细胞介素(IL)-2、IL-4、IL-6、IL-10、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、IL-17A的水平,比较上述指标在两组之间的差异。结果与配方奶喂养组比较,母乳喂养组婴儿外周血的Th1百分比(t=3.038)、Treg百分比(t=2.088)、Th1/Th2(Z=2.756)、IL-10(Z=2.297)及IFN-γ(Z=2.076)较高,Th17百分比(Z=2.704)、IL-17A(t=2.187)较低,差异均有统计学意义(P<0.05);两组间Th2百分比、IL-2、IL-4、IL-6、TNF-α水平差异无统计学意义(P>0.05)。结论母乳喂养对婴儿CD4⁺T淋巴细胞免疫反应的调节作用表现为促进Th1/Th2向Th1方向发展以及Treg的免疫调节作用,但抑制Th17型免疫反应,这说明母乳整体成分有助于婴儿免疫系统发育成熟,增强免疫防御和免疫耐受。

关键词: 母乳喂养, 获得性免疫, CD4⁺T淋巴细胞, 辅助性T淋巴细胞, 调节性T淋巴细胞

CLC Number:

R174.4

ZHU Simin, TU Wenjuan, ZHANG Wenting, TU Ziqi, WANG Cheng'an. Effects of breastfeeding on immune response of CD4⁺T lymphocytes in infants[J]. Chinese Journal of Child Health Care, 2024, 32(1): 103-107.

朱思敏, 屠文娟, 张雯婷, 屠子骐, 汪骋安. 母乳喂养对婴儿CD4⁺T淋巴细胞免疫反应的影响[J]. 中国儿童保健杂志, 2024, 32(1): 103-107.

References

[1] Lyons KE, Ryan CA, Dempsey EM, et al. Breast milk, a source of beneficial microbes and associated benefits for infant health[J]. Nutrients, 2020, 12(4): 1039.
[2] Chin N, Mendez-Lagares G, Taft DH, et al. Transient effect of infant formula supplementation on the intestinal microbiota[J]. Nutrients, 2021, 13(3): 807.
[3] Acevedo N, Alashkar Alhamwe B, Caraballo L, et al. Perinatal and early-life nutrition, epigenetics, and allergy[J]. Nutrients, 2021, 13(3): 724.
[4] Le Doare K, Holder B, Bassett A, et al. Mother's milk: A purposeful contribution to the development of the infant microbiota and immunity[J]. Front Immunol, 2018, 9: 361.
[5] 李在玲,张婷,陈同辛,等. 肠道微生态与婴幼儿免疫[J].临床儿科杂志, 2020, 38(11): 801-809,816.
Li ZL, Zhang T, Chen TX, et al. Intestinal microecology and infant immunity[J].J Clin Pediat, 2020, 38(11): 801-809,816.(in Chinese)
[6] Kononova S, Litvinova E, Vakhitov T, et al. Acceptive immunity: The role of fucosylated glycans in human host-microbiome interactions[J]. Int J Mol Sci, 2021, 22(8): 3854.
[7] Fujimura T, Lum SZC, Nagata Y, et al. Influences of maternal factors over offspring allergies and the application for food allergy[J]. Front Immunol, 2019, 10: 1933.
[8] Verhasselt V. Breastfeeding, a personalized medicine with influence on short- and long-term immune health[J]. Nestle Nutr Inst Workshop Ser, 2020, 94: 48-58.
[9] Hundshammer C, Minge O. In love with shaping you-influential factors on the breast milk content of human milk oligosaccharides and their decisive roles for neonatal development[J]. Nutrients, 2020, 12(11): 3568.
[10] Asarat M, Apostolopoulos V, Vasiljevic T, et al. Short-chain fatty acids regulate cytokines and Th17/Treg cells in human peripheral blood mononuclear cells in vitro[J]. Immunol Invest, 2016, 45(3): 205-222.
[11] Li N, Xie Q, Zhao L, et al. Human milk and infant formula modulate the intestinal microbiota and immune systems of human microbiota-associated mice[J]. Food Funct, 2021, 12(6): 2784-2798.
[12] Kaiko GE, Horvat JC, Beagley KW, et al. Immunological decision-making: How does the immune system decide to mount a helper T-cell response?[J]. Immunology, 2008, 123(3): 326-338.
[13] Butcher MJ, Zhu J. Recent advances in understanding the Th1/Th2 effector choice[J]. Fac Rev, 2021, 10: 30.
[14] Packi K, Matysiak J, Klimczak S, et al. Analysis of the serum profile of cytokines involved in the T-helper cell type 17 immune response pathway in atopic children with food allergy[J]. Int J Environ Res Public Health, 2022, 19(13): 7877.
[15] Cukrowska B, Bierla JB, Zakrzewska M, et al. The relationship between the infant gut microbiota and allergy. The role of bifidobacterium breve and prebiotic oligosaccharides in the activation of anti-allergic mechanisms in early life[J]. Nutrients, 2020, 12(4): 946.
[16] Liu P, Hu T, Kang C, et al. Research advances in the treatment of allergic rhinitis by probiotics[J]. J Asthma Allergy, 2022, 15: 1413-1428.
[17] Lauren Y. Immunologic properties of human milk and clinical implications in the neonatal population[J]. NeoReviews, 2020, 21(12): e809-e816
[18] 张萌, 李文星, 唐军. 母乳中生物活性物质对婴儿生长发育影响的研究进展[J].中国当代儿科杂志, 2020, 22(1): 82-87.
Zhang M, Li WX, Tang J. Research advances in the effect of bioactive substances in breast milk on the growth and development of infants[J].Chin J Contemp Pediatr, 2020, 22(1): 82-87. (in Chinese)
[19] West CE, Kvistgaard AS, Peerson JM, et al.Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life:A randomized controlled trial[J]. Pediatr Res, 2017, 82(1): 63-71.
[20] Lonnerdal B, Kvistgaard AS, Peerson JM, et al. Growth, nutrition, and cytokine response of breast-fed infants and infants fed formula with added bovine osteopontin[J]. J Pediatr Gastroenterol Nutr, 2016, 62(4): 650-657.
[21] Melnik BC, Schmitz G. Milk's role as an epigenetic regulator in health and disease[J]. Diseases, 2017, 5(1): 12.
[22] He KJ, Dong JH, Ouyang XM, et al. Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota[J]. Front Nutr, 2022, 9: 911315.
[23] 金紫璇, 盛晓阳. 人乳低聚糖对婴儿肠道菌群影响的研究进展[J].中华实用儿科临床杂志, 2022, 37(3): 227-230.
Jin ZX, ShengXY.Research progress on the effects of human milk oligosaccharides on infant intestinal flora[J].Chin J Appl Clin Pediat, 2022, 37(3): 227-230.(in Chinese)
[24] Quin C, Vicaretti SD, Mohtarudin NA, et al. Influence of sulfonated and diet-derived human milk oligosaccharides on the infant microbiome and immune markers[J]. J Biol Chem, 2020, 295(12): 4035-4048.
[25] He Y, Liu S, Kling DE, et al. The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation[J]. Gut, 2016, 65(1): 33-46.
[26] Fibbiani M, Ghelli Luserna DIRL, Novelli T, et al. The impact of human milk oligosaccharides on health from infancy to childhood[J]. Minerva Pediatr (Torino), 2022, 74(6): 724-732.
[27] Donovan SM, Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity[J]. Ann Nutr Metab, 2016, 69 (Suppl 2): 42-51.
[28] van Stigt AH, Oude Rengerink K, Bloemenkamp KWM, et al. Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort[J]. BMC Infect Dis, 2022, 22(1): 152.
[29] Tundup S, Srivastava L, Norberg T, et al. A neoglycoconjugate containing the human milk sugar LNFP III drives anti-inflammatory activation of antigen presenting cells in a CD14 dependent pathway[J]. PLoS One, 2015, 10(9): e0137495.
[30] Macchiaverni P, Rekima A, Turfkruyer M, et al. Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma[J]. Allergy, 2014, 69(3): 395-398.
[31] Bouchaud G, Castan L, Chesne J, et al. Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice[J]. Allergy, 2016, 71(1): 68-76.