DOI QR코드

DOI QR Code

CD4+/CD8+ T lymphocytes imbalance in children with severe 2009 pandemic influenza A (H1N1) pneumonia

  • Kim, Ji-Eun (Department of Pediatrics, Korea University Anam Hospital) ;
  • Bauer, Siegfried (Department of Pediatrics, Korea University Anam Hospital) ;
  • La, Kyong-Suk (Department of Pediatrics, Korea University Anam Hospital) ;
  • Lee, Kee-Hyoung (Department of Pediatrics, Korea University Anam Hospital) ;
  • Choung, Ji-Tae (Department of Pediatrics, Korea University Anam Hospital) ;
  • Roh, Kyoung-Ho (Department of Laboratory Medicine, Korea University Anam Hospital) ;
  • Lee, Chang-Kyu (Department of Laboratory Medicine, Korea University Anam Hospital) ;
  • Yoo, Young (Department of Pediatrics, Korea University Anam Hospital)
  • Received : 2011.01.22
  • Accepted : 2011.05.06
  • Published : 2011.05.15

Abstract

Purpose: This study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1) pneumonia, and to compare their clinical and immunological findings with those of control subjects. Methods: Thirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group), 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group) and 13 control subjects (control group) were measured. Results: Total lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02). The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group ($411.5{\pm}253.5/{\mu}L$) than in the moderate pneumonia ($644.9{\pm}291.1/{\mu}L$, P=0.04) and control ($902.5{\pm}461.2/{\mu}L$, P=0.01) groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group ($684.2{\pm}420.8/{\mu}L$) than in the moderate pneumonia ($319.7{\pm}176.6/{\mu}L$, P=0.02) and control ($407.2{\pm}309.3/{\mu}L$, P=0.03) groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group ($0.86{\pm}0.24$) than in the moderate pneumonia ($1.57{\pm}0.41$, P=0.01) and control ($1.61{\pm}0.49$, P=0.01) groups. The serum levels of immunoglobulin G, immunoglobulin M and immunoglobulin E were significantly higher in the severe pneumonia group than in the 2 other groups. Conclusion: The results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children.

Keywords

References

  1. Chan M. World now at the start of 2009 influenza pandemic [Internet]. Geneva: World Health Organization; c2011 [cited 2011 Mon Date]. Available from: http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html.
  2. Miroballi Y, Baird JS, Zackai S, Cannon JM, Messina M, Ravindranath T, et al. Novel influenza A(H1N1) in a pediatric health care facility in New York City during the first wave of the 2009 pandemic. Arch Pediatr Adolesc Med 2010;164:24-30. https://doi.org/10.1001/archpediatrics.2009.259
  3. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605-15. https://doi.org/10.1056/NEJMoa0903810
  4. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009;361:680-9. https://doi.org/10.1056/NEJMoa0904252
  5. Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A (H1N1) infection in California. JAMA 2009;302:1896-902. https://doi.org/10.1001/jama.2009.1583
  6. Cui W, Zhao H, Lu X, Wen Y, Zhou Y, Deng B, et al. Factors associated with death in hospitalized pneumonia patients with 2009 H1N1 influenza in Shenyang, China. BMC Infect Dis 2010;10:145. https://doi.org/10.1186/1471-2334-10-145
  7. Giamarellos-Bourboulis EJ, Raftogiannis M, Antonopoulou A, Baziaka F, Koutoukas P, Savva A, et al. Effect of the novel influenza A (H1N1) virus in the human immune system. PLoS One 2009;4:e8393. https://doi.org/10.1371/journal.pone.0008393
  8. Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity 2006;24:5-9. https://doi.org/10.1016/j.immuni.2005.12.005
  9. Doherty PC. Cytotoxic T cell effector and memory function in viral immunity. Curr Top Microbiol Immunol 1996;206:1-14.
  10. Mauad T, Hajjar LA, Callegari GD, da Silva LF, Schout D, Galas FR, et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med 2010;181:72-9. https://doi.org/10.1164/rccm.200909-1420OC
  11. Bruder D, Srikiatkhachorn A, Enelow RI. Cellular immunity and lung injury in respiratory virus infection. Viral Immunol 2006;19:147-55. https://doi.org/10.1089/vim.2006.19.147
  12. Jadavji T, Law B, Lebel MH, Kennedy WA, Gold R, Wang EE. A practical guide for the diagnosis and treatment of pediatric pneumonia. CMAJ 1997;156:S703-11.
  13. Nichols JE, Niles JA, Roberts NJ Jr. Human lymphocyte apoptosis after exposure to influenza A virus. J Virol 2001;75:5921-9. https://doi.org/10.1128/JVI.73.13.5921-5929.2001
  14. Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen VC, et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 2004;350:1179-88. https://doi.org/10.1056/NEJMoa040419
  15. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005;11:201-9. https://doi.org/10.3201/eid1102.041061
  16. Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, et al. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol 2010;84:6527-35. https://doi.org/10.1128/JVI.00519-10
  17. Moskophidis D, Kioussis D. Contribution of virus-specific CD8+ cytotoxic T cells to virus clearance or pathologic manifestations of influenza virus infection in a T cell receptor transgenic mouse model. J Exp Med 1998;188:223-32. https://doi.org/10.1084/jem.188.2.223
  18. Robinson M, O'Donohoe J, Dadian G, Wankowicz A, Barltrop D, Hobbs JR. An analysis of the normal ranges of lymphocyte subpopulations in children aged 5-13 years. Eur J Pediatr 1996;155:535-9.
  19. Libster R, Bugna J, Coviello S, Hijano DR, Dunaiewsky M, Reynoso N, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med 2010;362:45-55. https://doi.org/10.1056/NEJMoa0907673

Cited by

  1. A/H1N1 infection: immunological parameters in ICU patients vol.16, pp.suppl1, 2011, https://doi.org/10.1186/cc10620
  2. Development of Cross-Protective Influenza A Vaccines Based on Cellular Responses vol.6, pp.None, 2011, https://doi.org/10.3389/fimmu.2015.00237
  3. Literature review and future strategies of childhood respiratory diseases in Korea vol.6, pp.suppl1, 2018, https://doi.org/10.4168/aard.2018.6.s1.s66
  4. Erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-κB and p38 MAPK pathway vol.10, pp.2, 2011, https://doi.org/10.1016/j.jpha.2019.09.005
  5. β-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling vol.41, pp.9, 2020, https://doi.org/10.1038/s41401-020-0403-9