Skip to main content
Log in

Changes in Fetal Thymic Immune Cell Populations in a Sheep Model of Intrauterine Inflammation

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Intrauterine inflammation is a common antecedent of preterm birth and can alter the development of the fetal thymus, the site of development, and maturation of T lymphocytes. The effects of intrauterine inflammation on specific thymic T lymphocyte populations are largely unknown. We hypothesized that intrauterine inflammation would alter fetal thymic T cell populations. Immunohistochemistry was used to quantitate the relative proportions of thymic cortical and medullary cell populations in fetal sheep 7 days after intra-amniotic lipopolysaccharide (LPS) injection. The proportions of CD8+and MHC II+ cells in the fetal thymus were reduced in response to LPS. The ratio of CD4:CD8 cells was increased by LPS exposure. No changes were observed in the percentage of CD4+, γδ(WC1)+, CD45R+B cells, or CD44+ cells. These studies indicate that intrauterine inflammation impacts thymic composition of CD8 T cells and the development and/or activation of CD4 T cells in the fetal thymus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wong P, Pamer EG. CD8 T cell responses to infectious pathogens. Annu Rev Immunol. 2003;21:29–70

    Article  CAS  PubMed  Google Scholar 

  2. Clark EA, Ledbetter JA. How B and T cells talk to each other. Nature. 1994;367(6462):425–428

    Article  CAS  PubMed  Google Scholar 

  3. Elmore SA. Enhanced histopathology of the thymus. Toxicol Pathol. 2006;34(5):656–665

    Article  PubMed  PubMed Central  Google Scholar 

  4. Toti P, De Felice C, Stumpo M, et al. Acute thymic involution in fetuses and neonates with chorioamnionitis. Hum Pathol. 2000;31(9):1121–1128

    Article  CAS  PubMed  Google Scholar 

  5. Fahey JO. Clinical management of intra-amniotic infection and chorioamnionitis: a review of the literature. J Midwifery Women’s Health. 2008;53(3):227–235

    Article  Google Scholar 

  6. Goldenberg RL, Culhane JF. Infection as a cause of preterm birth. Clin Perinatol. 2003;30(4):677–700

    Article  PubMed  Google Scholar 

  7. Guzick DS, Winn K. The association of chorioamnionitis with preterm delivery. Obstet Gynecol. 1985;65(1):11–16

    CAS  PubMed  Google Scholar 

  8. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–1507

    Article  CAS  PubMed  Google Scholar 

  9. Moss TJM, Nitsos I, Kramer BW, Ikegami M, Newnham JP, Jobe AH. Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep. Am J Obstet Gynecol. 2002;187(4):1059–1065

    Article  CAS  PubMed  Google Scholar 

  10. Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clin Obstet Gynecol. 2007;50(3):652–683

    Article  PubMed  Google Scholar 

  11. Moss TJM, Nitsos I, Ikegami M, Jobe AH, Newnham JP. Experimental intrauterine Ureaplasma infection in sheep. Am J Obstet Gynecol. 2005;192(4):1179–1186

    Article  PubMed  Google Scholar 

  12. Moss TJM, Nitsos I, Knox CL, et al. Ureaplasma colonization of amniotic fluid and efficacy of antenatal corticosteroids for preterm lung maturation in sheep. Am J Obstet Gynecol. 2009;200(1):96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009;200(4):372. e371–e376

    Article  Google Scholar 

  14. Duncan JR, Cock ML, Suzuki K, Scheerlinck JPY, Harding R, Rees SM. Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence of hypoxemia. J Soc Gynecol Investig. 2006;13(2):87–96

    Article  CAS  PubMed  Google Scholar 

  15. Wolfs TGAM, Buurman WA, Zoer B, et al. Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep. PLoS One. 2009;4(6):e5837

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Romero R, Gotsch F, Pineles B, Kusanovic JP. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev. 2007;65(12 pt 2): S194–S202

    Article  PubMed  Google Scholar 

  17. Been JV, Rours IGIJG, Kornelisse RF, et al. Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. Am J Obstet Gynecol. 2009;201(6)587.

    Article  PubMed  CAS  Google Scholar 

  18. Di Naro E, Cromi A, Ghezzi F, et al. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome. Am J Obstet Gynecol. 2006;194(1):153–159

    Article  PubMed  Google Scholar 

  19. El-Haieg DO, Zidan AA, El-Nemr MM. The relationship between sonographic fetal thymus size and the components of the systemic fetal inflammatory response syndrome in women with preterm prelabour rupture of membranes. BJOG. 2008;115(7):836–841

    Article  CAS  PubMed  Google Scholar 

  20. Kunzmann S, Glogger K, Been JV, et al. Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep. Am J Obstet Gynecol. 2010;202(5):e1–e9

    Article  CAS  Google Scholar 

  21. Lee AJ, Lambermont VA, Pillow JJ, et al. Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep. Am J Obstet Gynecol. 2011;204(4):e17–e24

    Article  CAS  Google Scholar 

  22. Nitsos I, Moss TJM, Cock ML, Harding R, Newnham JP. Fetal responses to intra-amniotic endotoxin in sheep. J Soc Gynecol Investig. 2002;9(2):80–85

    Article  CAS  PubMed  Google Scholar 

  23. Jobe AH, Newnham JP, Willet KE, et al. Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol. Am J Respir Crit Care Med. 2000;162(5):1656–1661

    Article  CAS  PubMed  Google Scholar 

  24. Bischof RJ, Meeusen EN. Cellular kinetics of an allergic-type response in a sheep mammary gland model of inflammation. Clin Exp Allergy. 2002;32(4):619–626

    Article  CAS  PubMed  Google Scholar 

  25. Holder JE, Washington EA, Cunningham CP, Cahill RNP, Kimpton WG. Cell death and thymic export during fetal life. Eur J Immunol. 2006;36(10):2624–2631

    Article  CAS  PubMed  Google Scholar 

  26. Wu L, Kincade PW, Shortman K. The CD44 expressed on the earliest intrathymic precursor population functions as a thymus homing molecule but does not bind to hyaluronate. Immunol Lett. 1993;38(1):69–75

    Article  CAS  PubMed  Google Scholar 

  27. Kawakami N, Nishizawa F, Sakane N, et al. Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus. J Immunol. 1999;163(6):3211–3216

    CAS  PubMed  Google Scholar 

  28. Murphy DB, Lo D, Rath S, et al. A novel MHC class II epitope expressed in thymic medulla but not cortex. Nature. 1989;338(6218):765–768

    Article  CAS  PubMed  Google Scholar 

  29. Li W, Kim MG, Gourley TS, McCarthy BP, Sant’Angelo DB, Chang CH. An alternate pathway for CD4 T cell development: thymocyte-expressed MHC class II selects a distinct T cell population. Immunity. 2005;23(4):375–386

    Article  CAS  PubMed  Google Scholar 

  30. Min HS, Lee YJ, Jeon YK, et al. MHC class II-restricted interaction between thymocytes plays an essential role in the production of innate CD8+ T cells. J Immunol. 2011;186(10):5749–5757

    Article  CAS  PubMed  Google Scholar 

  31. Ghanem ENB, McElroy DS, D’Orazio SEF. Multiple mechanisms contribute to the robust rapid gamma interferon response by CD8+ T cells during Listeria monocytogenes infection. Infect Immun. 2009;77(4):1492–1501

    Article  CAS  Google Scholar 

  32. Komia-Koma M, Gildchrist DS, Xu D. Direct recognition of LPS by human but not murine CD8+ T cells via TLR4 complex. Euro J Immunol. 2009;39(6):1564–1572

    Article  CAS  Google Scholar 

  33. Chen C, Herzig CTA, Telfer JC, Baldwin CL. Antigenic basis of diversity in the γδ T cell co-receptor WC1 family. Mol Immunol. 2009;46(13):2565–2575

    Article  CAS  PubMed  Google Scholar 

  34. Wang F, Herzig C, Ozer D, Baldwin CL, Telfer JC. Tyrosine phosphorylation of scavenger receptor cysteine-rich WC1 is required for the WC1-mediated potentiation of TCR-induced T-cell proliferation. Euro J Immunol. 2009;39(1):254–266

    Article  CAS  Google Scholar 

  35. Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol. 2009;29(2):79–88

    Article  CAS  PubMed  Google Scholar 

  36. Keski-Nisula L, Katila ML, Remes S, Heinonen S, Pekkanen J. Intrauterine bacterial growth at birth and risk of asthma and allergic sensitization among offspring at the age of 15 to 17 years. J Allergy Clin Immunol. 2009;123(6):1305–1311

    Article  PubMed  Google Scholar 

  37. Kumar R, Yu Y, Story RE, et al. Prematurity, chorioamnionitis, and the development of recurrent wheezing: A prospective birth cohort study. J Allergy Clin Immunol. 2008;121(4):878–884

    Article  PubMed  PubMed Central  Google Scholar 

  38. Murthy V, Kennea NL. Antenatal infection/inflammation and fetal tissue injury. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):479–489

    Article  PubMed  Google Scholar 

  39. Moss TJM, Davey MG, Harding R, Newnham JP. Effects of intraamniotic endotoxin on lung structure and function two months after term birth in sheep. J Soc Gynecol Investig. 2002;9(4):220–225

    Article  CAS  PubMed  Google Scholar 

  40. Kallapur SG, Jobe AH, Ball MK, et al. Pulmonary and systemic endotoxin tolerance in preterm fetal sheep exposed to chorioamnionitis. J Immunol. 2007;179(12):8491–8499

    Article  CAS  PubMed  Google Scholar 

  41. Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH. Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. Am J Respir Crit Care Med. 2005;171(1):73–77

    Article  PubMed  Google Scholar 

  42. Lee SE, Romero R, Jung H, Park CW, Park JS, Yoon BH. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2007;197(3):294. e291–e296

    Google Scholar 

  43. Park CW, Moon KC, Park JS, Jun JK, Yoon BH. The frequency and clinical significance of intra-uterine infection and inflammation in patients with placenta previa and preterm labor and intact membranes. Placenta. 2009;30(7):613–618

    Article  CAS  PubMed  Google Scholar 

  44. Nitsos I, Rees SM, Duncan J, et al. Chronic exposure to intraamniotic lipopolysaccharide affects the ovine fetal brain. J Soc Gynecol Investig. 2006;13(4):239–247

    Article  CAS  PubMed  Google Scholar 

  45. Kramer BW, Joshi SN, Moss TJM, et al. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L345–L353

    Article  CAS  PubMed  Google Scholar 

  46. Toti P, De Felice C, Occhini R, et al. Spleen depletion in noenatal sepsis and chorioamnionitis. Am J Clin Pathol. 2004;122(5):765–771

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jacqueline M. Melville BSc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melville, J.M., Bischof, R.J., Meeusen, E.N. et al. Changes in Fetal Thymic Immune Cell Populations in a Sheep Model of Intrauterine Inflammation. Reprod. Sci. 19, 740–747 (2012). https://doi.org/10.1177/1933719111432873

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719111432873

Keywords

Navigation