Unique Characteristics of Neonatal T Cells
Main Article Content
Abstract
Birth causes complex changes in the individual physiology and organ systems and certainly poses a big immune challenge. The sudden encounter with an antigen full world, with the exposure to food antigens, and the colonization of the skin and mucosa with microbiota, require a tolerant immune system. Nevertheless, neonates must also be able to deal with pathogens, which makes their immune system unique.
T lymphocytes are responsible for the coordination of the adaptive immune system response, the elimination of infected cells and the type of immune response and memory. It has been shown that neonatal cells have intrinsic differences with adult cells, biased towards an innate response and a tolerant phenotype.
In the perinatal period, the immune system changes from basal signaling and innate like responses, towards stimulus-specific signals, which increase with gestational age. After birth the cells of the immune system continue to change both in composition and function.
In this review, we present the intrinsic differences of neonatal CD4+ and CD8+ T cells, as compared with adult naïve cells. A specific transcriptome profile is present in both CD4+ and CD8+ neonatal T cells, with overexpression of homeobox transcription factors. These cells also present differences in cell signaling and metabolic characteristics, which result in unique functional capabilities. Neonatal CD4+ T cells respond differently from adult cells, with a high production of IL-8, a prevalent Th2 over Th1 profile, and an innate inflammatory response.
The neonatal period is one of the most vulnerable periods of life, with a high morbidity and mortality rate, approaching on average 17 deaths per 1000 live births worldwide. A better understanding of the neonatal immune system will help to ensure a better care of this vulnerable population.
Article Details
How to Cite
A., Kempis-Calanis L. et al.
Unique Characteristics of Neonatal T Cells.
Medical Research Archives, [S.l.], v. 11, n. 1, jan. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3568>. Date accessed: 23 apr. 2024.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. PrabhuDas M, Adkins B, Gans H, et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. Mar 2011;12(3):189-94. doi:10.1038/ni0311-189
3. (https://www.unicef.org/reports/levels-and-trends-child-mortality-report-2019). Levels and trends in child mortality report.
4. Peterson LS, Hedou J, Ganio EA, et al. Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum. Front Immunol. 2021;12:714090. doi:10.3389/fimmu.2021.714090
5. Tosato F, Bucciol G, Pantano G, et al. Lymphocytes subsets reference values in childhood. Cytometry A. Jan 2015;87(1):81-5. doi:10.1002/cyto.a.22520
6. Upham JW, Lee PT, Holt BJ, et al. Development of interleukin-12-producing capacity throughout childhood. Infect Immun. Dec 2002;70(12):6583-8. doi:10.1128/IAI.70.12.6583-6588.2002
7. Wang X, Mou W, Qi Z, et al. Neonates are armed with deviated immune cell proportion and cytokine reduction but higher T cell proliferation potentiality. Acta Biochim Biophys Sin (Shanghai). Sep 1 2018;50(9):934-937. doi:10.1093/abbs/gmy079
8. Galindo-Albarran AO, Lopez-Portales OH, Gutierrez-Reyna DY, et al. CD8(+) T Cells from Human Neonates Are Biased toward an Innate Immune Response. Cell Rep. Nov 15 2016;17(8):2151-2160. doi:10.1016/j.celrep.2016.10.056
9. Gutierrez-Reyna DY, Cedillo-Banos A, Kempis-Calanis LA, et al. IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8(+) T Cells. Front Immunol. 2020;11:1089. doi:10.3389/fimmu.2020.01089
10. Razzaghian HR, Sharafian Z, Sharma AA, et al. Neonatal T Helper 17 Responses Are Skewed Towards an Immunoregulatory Interleukin-22 Phenotype. Front Immunol. 2021;12:655027. doi:10.3389/fimmu.2021.655027
11. Rudd BD. Neonatal T Cells: A Reinterpretation. Annu Rev Immunol. Apr 26 2020;38:229-247. doi:10.1146/annurev-immunol-091319-083608
12. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. Apr 2013;13(4):227-42. doi:10.1038/nri3405
13. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. Jul 2015;74(1):5-17. doi:10.1016/j.cyto.2014.09.011
14. Takase K, Saito T. [T cell activation]. Ryumachi. Oct 1995;35(5):853-61.
15. Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol. 2003;21:713-58. doi:10.1146/annurev.immunol.21.120601.140942
16. Licona-Limon P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol. Jun 2013;14(6):536-42. doi:10.1038/ni.2617
17. Chen J, Guan L, Tang L, et al. T Helper 9 Cells: A New Player in Immune-Related Diseases. DNA Cell Biol. Oct 2019;38(10):1040-1047. doi:10.1089/dna.2019.4729
18. Puerta-Arias JD, Mejia SP, Gonzalez A. The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses. Front Cell Infect Microbiol. 2020;10:595301. doi:10.3389/fcimb.2020.595301
19. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol. Aug 2009;10(8):857-63. doi:10.1038/ni.1767
20. Dowling MR, Kan A, Heinzel S, Marchingo JM, Hodgkin PD, Hawkins ED. Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny. Front Immunol. 2018;9:2461. doi:10.3389/fimmu.2018.02461
21. Rackaityte E, Halkias J. Mechanisms of Fetal T Cell Tolerance and Immune Regulation. Front Immunol. 2020;11:588. doi:10.3389/fimmu.2020.00588
22. Dammann O, O'Shea TM. Cytokines and perinatal brain damage. Clin Perinatol. Dec 2008;35(4):643-63, v. doi:10.1016/j.clp.2008.07.011
23. Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol. Sep 2007;50(3):652-83. doi:10.1097/GRF.0b013e31811ebef6
24. Vitoratos N, Papadias C, Economou E, Makrakis E, Panoulis C, Creatsas G. Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome. Mediators Inflamm. 2006;2006(4):30485. doi:10.1155/MI/2006/30485
25. Burt TD. Fetal regulatory T cells and peripheral immune tolerance in utero: implications for development and disease. Am J Reprod Immunol. Apr 2013;69(4):346-58. doi:10.1111/aji.12083
26. Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. May 2007;7(5):379-90. doi:10.1038/nri2075
27. Zaghouani H, Hoeman CM, Adkins B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol. Dec 2009;30(12):585-91. doi:10.1016/j.it.2009.09.002
28. Basha S, Surendran N, Pichichero M. Immune responses in neonates. Expert Rev Clin Immunol. Sep 2014;10(9):1171-84. doi:10.1586/1744666X.2014.942288
29. Das A, Rouault-Pierre K, Kamdar S, et al. Adaptive from Innate: Human IFN-gamma(+)CD4(+) T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults. J Immunol. Sep 1 2017;199(5):1696-1705. doi:10.4049/jimmunol.1700551
30. Connors TJ, Ravindranath TM, Bickham KL, et al. Airway CD8(+) T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection. Am J Respir Cell Mol Biol. Jun 2016;54(6):822-30. doi:10.1165/rcmb.2015-0297OC
31. Gibbons D, Fleming P, Virasami A, et al. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants. Nat Med. Oct 2014;20(10):1206-10. doi:10.1038/nm.3670
32. White GP, Watt PM, Holt BJ, Holt PG. Differential patterns of methylation of the IFN-gamma promoter at CpG and non-CpG sites underlie differences in IFN-gamma gene expression between human neonatal and adult CD45RO- T cells. J Immunol. Mar 15 2002;168(6):2820-7. doi:10.4049/jimmunol.168.6.2820
33. Bunis DG, Bronevetsky Y, Krow-Lucal E, et al. Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells. Cell Rep. Jan 5 2021;34(1):108573. doi:10.1016/j.celrep.2020.108573
34. Ng MSF, Roth TL, Mendoza VF, Marson A, Burt TD. Helios enhances the preferential differentiation of human fetal CD4(+) naive T cells into regulatory T cells. Sci Immunol. Nov 22 2019;4(41)doi:10.1126/sciimmunol.aav5947
35. Bermick JR, Issuree P, denDekker A, et al. Differences in H3K4me3 and chromatin accessibility contribute to altered T-cell receptor signaling in neonatal naive CD4 T cells. Immunol Cell Biol. Aug 2022;100(7):562-579. doi:10.1111/imcb.12561
36. Shi X, Ma W, Duan S, et al. Single-cell transcriptional diversity of neonatal umbilical cord blood immune cells reveals neonatal immune tolerance. Biochem Biophys Res Commun. Jun 11 2022;608:14-22. doi:10.1016/j.bbrc.2022.03.132
37. Sanchez-Villanueva JA, Rodriguez-Jorge O, Ramirez-Pliego O, et al. Contribution of ROS and metabolic status to neonatal and adult CD8+ T cell activation. PLoS One. 2019;14(12):e0226388. doi:10.1371/journal.pone.0226388
38. Siefker DT, Adkins B. Rapid CD8(+) Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen. Front Pediatr. 2016;4:141. doi:10.3389/fped.2016.00141
39. Zens KD, Chen JK, Guyer RS, et al. Reduced generation of lung tissue-resident memory T cells during infancy. J Exp Med. Oct 2 2017;214(10):2915-2932. doi:10.1084/jem.20170521
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