Is infant immunity actively suppressed or immature?

Virology: Research and Treatment

Volumn 5, Issue , 2014, Pages 1-9

  Gervassi, Ana L ^a   Horton, Helen ^a,b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b Department of Medicine ^*  (United States)

Author keywords

Immune suppression; Infant immunity; Infant vaccines

Indexed keywords

ARTICLE; B LYMPHOCYTE; CD5POS B CELL; DENDRITIC CELL; DRUG RESPONSE; HUMAN; IMMATURITY; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; INFANCY; INFANT; INFANT MORTALITY; INFECTION; MESENCHYMAL STROMA CELL; MYELOID DERIVED SUPPRESSOR CELL; NATURAL KILLER CELL; REGULATORY T LYMPHOCYTE; SUPPRESSOR CELL; VACCINATION;

EID: 84896876161     PISSN: None     EISSN: 1178122X     Source Type: Journal    
DOI: 10.4137/VRT.S12248     Document Type: Article

References (158)

1. WHO. Child Mortality Report. 2012; Geneva: World Health Organization.
2. Lozano R, Wang H, Foreman KJ, et al. Progress towards Millennium Development Goals 4 and 5 on maternal and child mortality: an updated systematic analysis. Lancet. 2011;378(9797):1139-1165.
3. Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis. 2008;8(8):498-510.
4. Snow RW, Korenromp EL, Gouws E. Pediatric mortality in Africa: plasmodium falciparum malaria as a cause or risk? Am J Trop Med Hyg. 2004;71(2 Suppl):16-24.
5. Chakraborty R. HIV-1 infection in children: a clinical and immunologic overview. Curr HIV Res. 2005;3(1):31-41.
6. Tu W, Chen S, Sharp M, et al. Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol. 2004;172(5):3260-3267.
7. Burchett SK, Corey L, Mohan KM, Westall J, Ashley R, Wilson CB. Diminished interferon-gamma and lymphocyte proliferation in neonatal and postpartum primary herpes simplex virus infection. J Infect Dis. 1992;165(5):813-818.
8. Gantt S, Muller WJ. The immunologic basis for severe neonatal herpes disease and potential strategies for therapeutic intervention. Clin Dev Immunol. 2013;2013:369172.
9. Lidehäll AK, Engman ML, Sund F, et al. Cytomegalovirus-specific CD4 and CD8 T cell responses in infants and children. Scand J Immunol. 2013;77(2):135-143.
10. Sullender WM, Miller JL, Yasukawa LL, et al. Humoral and cell-mediated immunity in neonates with herpes simplex virus infection. J Infect Dis. 1987;155(1):28-37.
11. Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342(4):225-231.
12. McIntyre P, Wood N. Pertussis in early infancy: disease burden and preventive strategies. Curr Opin Infect Dis. 2009;22(3):215-223.
13. Gantt S, Yao L, Kollmann TR, Casper C, Zhang J, Self SG. Implications of age-dependent immune responses to enterovirus-71 infection for disease pathogenesis and vaccine design. J Paed Infect Dis. 2013;2(2):162-170.
14. Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375(9725):1545-1555.
15. Ploin D, Chidiac C, Carrat F, et al; Fluco study group. Complications and factors associated with severity of influenza in hospitalized children and adults during the pandemic wave of A(H1N1)pdm 2009 infections-The Fluco French cohort. J Clin Virol. 2013;58(1):114-119.
16. Demirjian A, Levy O. Safety and efficacy of neonatal vaccination. Eur J Immunol. 2009;39(1):36-46.
17. Wood N, Siegrist CA. Neonatal immunization: where do we stand? Curr Opin Infect Dis. 2011;24(3):190-195.
18. PrabhuDas M, Adkins B, Gans H, et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011;12(3):189-194.
19. Labeaud AD, Malhotra I, King MJ, King CL, King CH. Do antenatal parasite infections devalue childhood vaccination? PLoS Negl Trop Dis. 2009;3(5):e442.
20. Wilson CB, Kollmann TR. Induction of antigen-specific immunity in human neonates and infants. Nestle Nutr Workshop Ser Pediatr Program. 2008;61:183-195.
21. Siegrist CA. The challenges of vaccine responses in early life: selected examples. J Comp Pathol. 2007;137 Suppl 1:S4-S9.
22. van den Biggelaar AH, Pomat W, Bosco A, et al. Pneumococcal conjugate vaccination at birth in a high-risk setting: no evidence for neonatal T-cell tolerance. Vaccine. 2011;29(33):5414-5420.
23. Vekemans J, Ota MO, Wang EC, et al. T cell responses to vaccines in infants: defective IFNgamma production after oral polio vaccination. Clin Exp Immunol. 2002;127(3):495-498.
24. Zaghouani H, Hoeman CM, Adkins B. Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells. Trends Immunol. 2009;30(12):585-591.
25. Ota MO, Vekemans J, Schlegel-Haueter SE, et al. Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults. Vaccine. 2004;22(3-4):511-519.
26. Wang G, Miyahara Y, Guo Z, Khattar M, Stepkowski SM, Chen W. "Default" generation of neonatal regulatory T cells. J Immunol. 2010;185(1):71-78.
27. Ota MO, Vekemans J, Schlegel-Haueter SE, et al. Influence of Mycobacterium bovis bacillus Calmette-Guérin on antibody and cytokine responses to human neonatal vaccination. J Immunol. 2002;168(2):919-925.
28. Weir RE, Gorak-Stolinska P, Floyd S, et al. Persistence of the immune response induced by BCG vaccination. BMC Infect Dis. 2008;8:9.
29. Lalor MK, Smith SG, Floyd S, et al. Complex cytokine profiles induced by BCG vaccination in UK infants. Vaccine. 2010;28(6):1635-1641.
30. Vekemans J, Amedei A, Ota MO, et al. Neonatal bacillus Calmette-Guérin vaccination induces adult-like IFN-gamma production by CD4+ T lymphocytes. Eur J Immunol. 2001;31(5):1531-1535.
31. Tena-Coki NG, Scriba TJ, Peteni N, et al. CD4 and CD8 T-cell responses to mycobacterial antigens in African children. Am J RespirCrit Care Med. 2010;182(1):120-129.
32. Lalor MK, Ben-Smith A, Gorak-Stolinska P, et al. Population differences in immune responses to Bacille Calmette-Guérin vaccination in infancy. J Infect Dis. 2009;199(6):795-800.
33. Lalor MK, Floyd S, Gorak-Stolinska P, et al. BCG vaccination induces different cytokine profiles following infant BCG vaccination in the UK and Malawi. J Infect Dis. 2011;204(7):1075-1085.
34. Kollmann TR, Reikie B, Blimkie D, et al. Induction of protective immunity to Listeria monocytogenes in neonates. J Immunol. 2007;178(6):3695-3701.
35. De Wit D, Tonon S, Olislagers V, et al. Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood. J Autoimmun. 2003;21(3):277-281.
36. Jullien P, Cron RQ, Dabbagh K, et al. Decreased CD154 expression by neonatal CD4+ T cells is due to limitations in both proximal and distal events of T cell activation. Int Immunol. 2003;15(12):1461-1472.
37. Goriely S, Van Lint C, Dadkhah R, et al. A defect in nucleosome remodeling prevents IL-12(p35) gene transcription in neonatal dendritic cells. J Exp Med. 2004;199(7):1011-1016.
38. Kollmann TR, Crabtree J, Rein-Weston A, et al. Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol. 2009;183(11):7150-7160.
39. Renneson J, Dutta B, Goriely S, et al. IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection. Eur J Immunol. 2009;39(10):2789-2799.
40. Lavoie PM, Huang Q, Jolette E, et al. Profound lack of interleukin (IL)-12/IL-23p40 in neonates born early in gestation is associated with an increased risk of sepsis. J Infect Dis. 2010;202(11):1754-1763.
41. Lewis DB. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Klein JO, Wilson CB, Baker CJ, Eds. Infectious Diseases of the Fetus and Newborn Infant, 6th Edition. 2006; Philadelphia: Elsevier Saunders; 25-128.
42. Marodi L. Innate cellular immune responses in newborns. Clin Immunol. 2006;118(2-3):137-144.
43. La Pine TR, Joyner JL, Augustine NH, Kwak SD, Hill HR. Defective production of IL-18 and IL-12 by cord blood mononuclear cells influences the T helper-1 interferon gamma response to group B Streptococci. Pediatr Res. 2003;54(2):276-281.
44. Krumbiegel D, Zepp F, Meyer CU. Combined Toll-like receptor agonists synergistically increase production of inflammatory cytokines in human neonatal dendritic cells. Hum Immunol. 2007;68(10):813-822.
45. Zucchini N, Crozat K, Baranek T, Robbins SH, Altfeld M, Dalod M. Natural killer cells in immunodefense against infective agents. Expert Rev Anti Infect Ther. 2008;6(6):867-885.
46. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503-510.
47. Verneris MR, Miller JS. The phenotypic and functional characteristics of umbilical cord blood and peripheral blood natural killer cells. Br J Haematol. 2009;147(2):185-191.
48. Guilmot A, Hermann E, Braud VM, Carlier Y, Truyens C. Natural killer cell responses to infections in early life. J Innate Immun. 2011;3(3):280-288.
49. Jacobson A, Bell F, Lejarcegui N, Mitchell C, Frenkel L, Horton H. Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity. PLoS One. 2013;8(6):e67700.
50. Gaddy J, Broxmeyer HE. Cord blood CD16+56-cells with low lytic activity are possible precursors of mature natural killer cells. Cell Immunol. 1997;180(2):132-142.
51. Hassan J, O'Neill S, O'Neill LA, Pattison U, Reen DJ. Signalling via CD28 of human naive neonatal T lymphocytes. Clin Exp Immunol. 1995;102(1):192-198.
52. Lewis DB, Yu CC, Meyer J, English BK, Kahn SJ, Wilson CB. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest. 1991;87(1):194-202.
53. Schultz C, Strunk T, Temming P, Matzke N, Härtel C. Reduced IL-10 production and-receptor expression in neonatal T lymphocytes. Acta Paediatr. 2007;96(8):1122-1125.
54. Ansart-Pirenne H, Soulimani N, Tartour E, Blot P, Sterkers G. Defective IL2 gene expression in newborn is accompanied with impaired tyrosine-phosphorylation in T cells. Pediatr Res. 1999;45(3):409-413.
55. Oriss TB, McCarthy SA, Campana MA, Morel PA. Evidence of positive cross-regulation on Th1 by Th2 and antigen-presenting cells: effects on Th1 induced by IL-4 and IL-12. J Immunol. 1999;162(4):1999-2007.
56. Miscia S, Di Baldassarre A, Sabatino G, et al. Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes. J Immunol. 1999;163(5):2416-2424.
57. Fitzpatrick DR, Wilson CB. Methylation and demethylation in the regulation of genes, cells, and responses in the immune system. Clin Immunol. 2003;109(1):37-45.
58. Gans HA, Yasukawa LL, Zhang CZ, et al. Effects of interleukin-12 and interleukin-15 on measles-specific T-cell responses in vaccinated infants. Viral Immunol. 2008;21(2):163-172.
59. Chen L, Cohen AC, Lewis DB. Impaired allogeneic activation and T-helper 1 differentiation of human cord blood naive CD4 T cells. Biol Blood Marrow Transplant. 2006;12(2):160-171.
60. Barbey C, Irion O, Helg C, et al. Characterisation of the cytotoxic alloresponse of cord blood. Bone Marrow Transplant. 1998;22 Suppl 1:S26-S30.
61. Slavcev A, Stríz I, Ivasková E, Breur-Vriesendorp BS. Alloresponses of cord blood cells in primary mixed lymphocyte cultures. Hum Immunol. 2002;63(3):155-163.
62. Berthou C, Legros-Maïda S, Soulié A, et al. Cord blood T lymphocytes lack constitutive perforin expression in contrast to adult peripheral blood T lymphocytes. Blood. 1995;85(6):1540-1546.
63. Rukavina D, Laskarin G, Rubesa G, et al. Age-related decline of perforin expression in human cytotoxic T lymphocytes and natural killer cells. Blood. 1998;92(7):2410-2420.
64. Migueles SA, Laborico AC, Shupert WL, et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol. 2002;3(11):1061-1068.
65. Schneider P. The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol. 2005;17(3):282-289.
66. Weller S, Braun MC, Tan BK, et al. Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104(12):3647-3654.
67. Kruschinski C, Zidan M, Debertin AS, von Hörsten S, Pabst R. Age-dependent development of the splenic marginal zone in human infants is associated with different causes of death. Hum Pathol. 2004;35(1):113-121.
68. Timens W, Boes A, Rozeboom-Uiterwijk T, Poppema S. Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J Immunol. 1989;143(10):3200-3206.
69. Capolunghi F, Cascioli S, Giorda E, et al. CpG drives human transitional B cells to terminal differentiation and production of natural antibodies. J Immunol. 2008;180(2):800-808.
70. Han P, McDonald T, Hodge G. Potential immaturity of the T-cell and antigen-presenting cell interaction in cord blood with particular emphasis on the CD40-CD40 ligand costimulatory pathway. Immunology. 2004;113(1):26-34.
71. Pihlgren M, Tougne C, Bozzotti P, et al. Unresponsiveness to lymphoid-mediated signals at the neonatal follicular dendritic cell precursor level contributes to delayed germinal center induction and limitations of neonatal antibody responses to T-dependent antigens. J Immunol. 2003;170(6):2824-2832.
72. Weitkamp JH, Lafleur BJ, Greenberg HB, Crowe JE. Natural evolution of a human virus-specific antibody gene repertoire by somatic hypermutation requires both hotspot-directed and randomly-directed processes. Hum Immunol. 2005;66(6):666-676.
73. Ridings J, Dinan L, Williams R, Roberton D, Zola H. Somatic mutation of immunoglobulin V(H)6 genes in human infants. Clin Exp Immunol. 1998;114(1):33-39.
74. Pihlgren M, Friedli M, Tougne C, Rochat AF, Lambert PH, Siegrist CA. Reduced ability of neonatal and early-life bone marrow stromal cells to support plasmablast survival. J Immunol. 2006;176(1):165-172.
75. Belnoue E, Pihlgren M, McGaha TL, et al. APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood. 2008;111(5):2755-2764.
76. Mastelic B, Kamath AT, Fontannaz P, et al. Environmental and T cell-intrinsic factors limit the expansion of neonatal follicular T helper cells but may be circumvented by specific adjuvants. J Immunol. 2012;189(12):5764-5772.
77. Lo YM, Lo ES, Watson N, et al. Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood. 1996;88(11):4390-4395.
78. Mold JE, Michaëlsson J, Burt TD, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science. 2008;322(5907):1562-1565.
79. Lissauer D, Piper K, Goodyear O, Kilby MD, Moss PA. Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity. J Immunol. 2012;189(2):1072-1080.
80. Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11(5):317-326.
81. Inada K, Shima T, Nakashima A, Aoki K, Ito M, Saito S. Characterization of regulatory T cells in decidua of miscarriage cases with abnormal or normal fetal chromosomal content. J Reprod Immunol. 2013;97(1):104-111.
82. Makrigiannakis A, Petsas G, Toth B, Relakis K, Jeschke U. Recent advances in understanding immunology of reproductive failure. J Reprod Immunol. 2011;90(1):96-104.
83. Quinn KH, Parast MM. Decidual regulatory T cells in placental pathology and pregnancy complications. Am J Reprod Immunol. 2013;69(6):533-538.
84. Ban Y, Chang Y, Dong B, Kong B, Qu X. Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal-maternal interface. J Int Med Res. 2013;41(4):1135-1149.
85. Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 2012;490(7418):102-106.
86. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+ CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod. 2004;10(5):347-353.
87. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology. 2004;112(1):38-43.
88. Fu B, Li X, Sun R, et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013;110(3):E231-E240.
89. Vacca P, Mingari MC, Moretta L. Natural killer cells in human pregnancy. J ReprodImmunol. 2013;97(1):14-19.
90. Amodio G, Mugione A, Sanchez AM, et al. HLA-G expressing DC-10 and CD4(+) T cells accumulate in human decidua during pregnancy. Hum Immunol. 2013;74(4):406-411.
91. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science. 2012;336(6086):1317-1321.
92. Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281(5380):1191-1193.
93. Lee JH, Lydon JP, Kim CH. Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability. Eur J Immunol. 2012;42(10):2683-2696.
94. Bansal AS, Bora SA, Saso S, Smith JR, Johnson MR, Thum MY. Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy. Expert Rev Clin Immunol. 2012;8(8):747-753.
95. Mao G, Wang J, Kang Y, et al. Progesterone increases systemic and local uterine proportions of CD4+ CD25+ Treg cells during midterm pregnancy in mice. Endocrinology. 2010;151(11):5477-5488.
96. Schumacher A, Heinze K, Witte J, et al. Human chorionic gonadotropin as a central regulator of pregnancy immune tolerance. J Immunol. 2013;190(6):2650-2658.
97. Tirado-González I, Freitag N, Barrientos G, et al. Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy. Mol Hum Reprod. 2013;19(1):43-53.
98. Blois SM, Ilarregui JM, Tometten M, et al. A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med. 2007;13(12):1450-1457.
99. Kim KH, Choi BK, Kim JD, et al. 4-1BB signaling breaks the tolerance of maternal CD8+ T cells that are reactive with alloantigens. PLoS One. 2012;7(9):e45481.
100. Riella LV, Dada S, Chabtini L, et al. B7h (ICOS-L) maintains tolerance at the fetomaternal interface. Am J Pathol. 2013;182(6):2204-2213.
101. Taglauer ES, Yankee TM, Petroff MG. Maternal PD-1 regulates accumulation of fetal antigen-specific CD8+ T cells in pregnancy. J ReprodImmunol. 2009;80(1-2):12-21.
102. D'Addio F, Riella LV, Mfarrej BG, et al. The link between the PDL1 costimulatory pathway and Th17 in fetomaternal tolerance. J Immunol. 2011;187(9):4530-4541.
103. Guleria I, Khosroshahi A, Ansari MJ, et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. J Exp Med. 2005;202(2):231-237.
104. Chabtini L, Mfarrej B, Mounayar M, et al. TIM-3 regulates innate immune cells to induce fetomaternal tolerance. J Immunol. 2013;190(1):88-96.
105. Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol. 2004;4(7):553-564.
106. Godfrey WR, Spoden DJ, Ge YG, et al. Cord blood CD4(+) CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood. 2005;105(2):750-758.
107. Takahata Y, Nomura A, Takada H, et al. CD25+ CD4+ T cells in human cord blood: an immunoregulatory subset with naive phenotype and specific expression of forkhead box p3 (Foxp3) gene. Exp Hematol. 2004;32(7):622-629.
108. Mackroth MS, Malhotra I, Mungai P, Koech D, Muchiri E, King CL. Human cord blood CD4+ CD25hi regulatory T cells suppress prenatally acquired T cell responses to Plasmodium falciparum antigens. J Immunol. 2011;186(5):2780-2791.
109. Hannet I, Erkeller-Yuksel F, Lydyard P, Deneys V, DeBruyère M. Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today. 1992;13(6):215, 218.
110. Lundell AC, Björnsson V, Ljung A, et al. Infant B cell memory differentiation and early gut bacterial colonization. J Immunol. 2012;188(9):4315-4322.
111. Baumgarth N, Herman OC, Jager GC, Brown LE, Herzenberg LA, Chen J. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J Exp Med. 2000;192(2):271-280.
112. Martin F, Oliver AM, Kearney JF. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity. 2001;14(5):617-629.
113. Sun CM, Fiette L, Tanguy M, Leclerc C, Lo-Man R. Ontogeny and innate properties of neonatal dendritic cells. Blood. 2003;102(2):585-591.
114. Borges-Almeida E, Milanez HM, Vilela MM, et al. The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns. BMC Infect Dis. 2011;11:38.
115. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162-174.
116. Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. Int Immunopharmacol. 2011;11(7):802-807.
117. Poschke I, Kiessling R. On the armament and appearances of human myeloid-derived suppressor cells. Clin Immunol. 2012;144(3):250-268.
118. Tacke RS, Lee HC, Goh C, et al. Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. Hepatology. 2012;55(2):343-353.
119. Vollbrecht T, Stirner R, Tufman A, et al. Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS. 2012;26(12):F31-F37.
120. Ioannou M, Alissafi T, Lazaridis I, et al. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol. 2012;188(3):1136-1146.
121. Montero AJ, Diaz-Montero CM, Kyriakopoulos CE, Bronte V, Mandruzzato S. Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother. 2012;35(2):107-115.
122. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253-268.
123. Poschke I, Mao Y, Adamson L, Salazar-Onfray F, Masucci G, Kiessling R. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines. Cancer Immunol Immunother. 2012;61(6):827-838.
124. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179(2):977-983.
125. Rieber N, Gille C, Köstlin N, et al. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin Exp Immunol. 2013;174(1):45-52.
126. Li H, Han Y, Guo Q, Zhang M, Cao X. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol. 2009;182(1):240-249.
127. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119 (Pt 11):2204-2213.
128. Srikanth GV, Tripathy NK, Nityanand S. Fetal cardiac mesenchymal stem cells express embryonal markers and exhibit differentiation into cells of all three germ layers. World J Stem Cells. 2013;5(1):26-33.
129. Javed MJ, Mead LE, Prater D, et al. Endothelial colony forming cells and mesenchymal stem cells are enriched at different gestational ages in human umbilical cord blood. Pediatr Res. 2008;64(1):68-73.
130. Nazarov I, Lee JW, Soupene E, et al. Multipotent stromal stem cells from human placenta demonstrate high therapeutic potential. Stem Cells Transl Med. 2012;1(5):359-372.
131. Karlsson H, Erkers T, Nava S, Ruhm S, Westgren M, Ringdén O. Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro. Clin Exp Immunol. 2012;167(3):543-555.
132. Siepe M, Thomsen AR, Duerkopp N, et al. Human neonatal thymus-derived mesenchymal stromal cells: characterization, differentiation, and immunomodulatory properties. Tissue Eng Part A. 2009;15(7):1787-1796.
133. Zhao ZG, Xu W, Sun L, et al. Immunomodulatory function of regulatory dendritic cells induced by mesenchymal stem cells. Immunol Invest. 2012;41(2):183-198.
134. Beyth S, Borovsky Z, Mevorach D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2005;105(5):2214-2219.
135. Chen HW, Chen HY, Wang LT, et al. Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines. J Immunol. 2013;190(10):5065-5077.
136. Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25 high FOXP3+ regulatory T cells. Stem Cells. 2008;26(1):212-222.
137. Ghannam S, Pène J, Torcy-Moquet G, Jorgensen C, Yssel H. Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J Immunol. 2010;185(1):302-312.
138. Luz-Crawford P, Kurte M, Bravo-Alegría J, et al. Mesenchymal stem cells generate a CD4+ CD25+ Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther. 2013;4(3):65.
139. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815-1822.
140. Rasmusson I, Ringdén O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation. 2003;76(8):1208-1213.
141. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101(9):3722-3729.
142. Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005;105(7):2821-2827.
143. Johann PD, Vaegler M, Gieseke F, et al. Tumour stromal cells derived from paediatric malignancies display MSC-like properties and impair NK cell cytotoxicity. BMC Cancer. 2010;10:501.
144. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. 2008;111(3):1327-1333.
145. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103(12):4619-4621.
146. Chen K, Wang D, Du WT, et al. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol. 2010;135(3):448-458.
147. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838-3843.
148. Levy O, Goriely S, Kollmann TR. Immune response to vaccine adjuvants during the first year of life. Vaccine. 2013;31(21):2500-2505.
149. Zoglmeier C, Bauer H, Nörenberg D, et al. CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res. 2011;17(7):1765-1775.
150. Shirota Y, Shirota H, Klinman DM. Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. J Immunol. 2012;188(4):1592-1599.
151. Lei J, Wang Z, Hui D, et al. Ligation of TLR2 and TLR4 on murine bone marrow-derived mesenchymal stem cells triggers differential effects on their immunosuppressive activity. Cell Immunol. 2011;271(1):147-156.
152. Dang Y, Wagner WM, Gad E, et al. Dendritic cell-activating vaccine adjuvants differ in the ability to elicit antitumor immunity due to an adjuvant-specific induction of immunosuppressive cells. Clin Cancer Res. 2012;18(11):3122-3131.
153. Benn CS. Combining vitamin A and vaccines: convenience or conflict? Dan Med J. 2012;59(1):B4378.
154. Villamor E, Fawzi WW. Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. Clin Microbiol Rev. 2005;18(3):446-464.
155. Yang WC, Ma G, Chen SH, Pan PY. Polarization and reprogramming of myeloid-derived suppressor cells. J Mol Cell Biol. 2013;5(3):207-209.
156. Najjar YG, Finke JH. Clinical perspectives on targeting of myeloid derived suppressor cells in the treatment of cancer. Front Oncol. 2013;3:49.
157. Mirza N, Fishman M, Fricke I, et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006;66(18):9299-9307.
158. Liu E, Law HK, Lau YL. BCG promotes cord blood monocyte-derived dendritic cell maturation with nuclear Rel-B up-regulation and cytosolic I kappa B alpha and beta degradation. Pediatr Res. 2003;54(1):105-112.