Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1998 May;94(1):109–114. doi: 10.1046/j.1365-2567.1998.00489.x

Fetal natural killer cell function is suppressed.

E Dominguez 1, J A Madrigal 1, Z Layrisse 1, S B Cohen 1
PMCID: PMC1364338  PMID: 9708194

Abstract

Previous studies have reported reduced natural killer (NK) cell activity in cord blood (CB) compared with adult blood mononuclear cell populations. Using a non-radioactive killing assay, we have verified these findings suggesting that either the fetal NK cell function is suppressed or that these cells are functionally immature. We have shown that CB NK cells are functional, since activating them with cytokines known to activate adult NK cells [interleukin-2 (IL-2), IL-12 and IL-15] increased activation. However, resting the cells, which enhanced adult NK cell activity (P < 0.01), had no effect on fetal NK cells (P = 0.2). These results suggested that fetal NK cells have the capacity to kill, but this is suppressed in vitro. This hypothesis was strengthened by our observation that eight of nine CB mononuclear cell populations had their NK activity restored by freeze-thawing, whereas four of five adult peripheral blood mononuclear cells had a reduced killing ability on freeze-thawing. Freeze-thawing removes a population of cells that suppresses CB NK cell function. To determine which was the case we performed extensive phenotypic analysis of the CB populations pre- and post-freezing and found that the percentage of the CD3- CD56+ population within CB increased significantly (P < 0.0005 by paired t-test) with freezing, whereas freeze-thawing had no effect on this population within a normal adult peripheral blood mononuclear cell population. Our data suggest that within CB there is a population of cells, as yet undefined, which may be inhibiting NK cell function. This report therefore shows clear differences between NK cells within the adult periphery and in CB, and may lead to a better understanding of events occurring in vivo.

Full text

PDF
109

Images in this article

112Figure 4
on p.112

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson P., Caligiuri M., Ritz J., Schlossman S. F. CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex. Nature. 1989 Sep 14;341(6238):159–162. doi: 10.1038/341159a0. [DOI] [PubMed] [Google Scholar]
  2. Bancroft G. J. The role of natural killer cells in innate resistance to infection. Curr Opin Immunol. 1993 Aug;5(4):503–510. doi: 10.1016/0952-7915(93)90030-v. [DOI] [PubMed] [Google Scholar]
  3. Beck R., Lam-Po-Tang P. R. Comparison of cord blood and adult blood lymphocyte normal ranges: a possible explanation for decreased severity of graft versus host disease after cord blood transplantation. Immunol Cell Biol. 1994 Oct;72(5):440–444. doi: 10.1038/icb.1994.65. [DOI] [PubMed] [Google Scholar]
  4. Bradstock K. F., Luxford C., Grimsley P. G. Functional and phenotypic assessment of neonatal human leucocytes expressing natural killer cell-associated antigens. Immunol Cell Biol. 1993 Dec;71(Pt 6):535–542. doi: 10.1038/icb.1993.59. [DOI] [PubMed] [Google Scholar]
  5. Carson W. E., Giri J. G., Lindemann M. J., Linett M. L., Ahdieh M., Paxton R., Anderson D., Eisenmann J., Grabstein K., Caligiuri M. A. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med. 1994 Oct 1;180(4):1395–1403. doi: 10.1084/jem.180.4.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cicuttini F. M., Martin M., Petrie H. T., Boyd A. W. A novel population of natural killer progenitor cells isolated from human umbilical cord blood. J Immunol. 1993 Jul 1;151(1):29–37. [PubMed] [Google Scholar]
  7. Domzig W., Stadler B. M., Herberman R. B. Interleukin 2 dependence of human natural killer (NK) cell activity. J Immunol. 1983 Apr;130(4):1970–1973. [PubMed] [Google Scholar]
  8. Ferrara J. L., Guillen F. J., van Dijken P. J., Marion A., Murphy G. F., Burakoff S. J. Evidence that large granular lymphocytes of donor origin mediate acute graft-versus-host disease. Transplantation. 1989 Jan;47(1):50–54. doi: 10.1097/00007890-198901000-00012. [DOI] [PubMed] [Google Scholar]
  9. Flomenberg N., Keever C. A. Cord blood transplants: potential utility and potential limitations. Bone Marrow Transplant. 1992;10 (Suppl 1):115–120. [PubMed] [Google Scholar]
  10. Fujino Y., Nakamura Y., Ueda K., Ozaki K., Ito F., Sun T. T., Umesaki N., Ogita S. Effects of serum from pregnant versus non-pregnant women on natural killer cell activity. Am J Reprod Immunol. 1997 May;37(5):365–367. doi: 10.1111/j.1600-0897.1997.tb00245.x. [DOI] [PubMed] [Google Scholar]
  11. Gaddy J., Risdon G., Broxmeyer H. E. Cord blood natural killer cells are functionally and phenotypically immature but readily respond to interleukin-2 and interleukin-12. J Interferon Cytokine Res. 1995 Jun;15(6):527–536. doi: 10.1089/jir.1995.15.527. [DOI] [PubMed] [Google Scholar]
  12. Gately M. K., Desai B. B., Wolitzky A. G., Quinn P. M., Dwyer C. M., Podlaski F. J., Familletti P. C., Sinigaglia F., Chizonnite R., Gubler U. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol. 1991 Aug 1;147(3):874–882. [PubMed] [Google Scholar]
  13. Gluckman E., Wagner J., Hows J., Kernan N., Bradley B., Broxmeyer H. E. Cord blood banking for hematopoietic stem cell transplantation: an international cord blood transplant registry. Bone Marrow Transplant. 1993 Mar;11(3):199–200. [PubMed] [Google Scholar]
  14. Griffin J. D., Hercend T., Beveridge R., Schlossman S. F. Characterization of an antigen expressed by human natural killer cells. J Immunol. 1983 Jun;130(6):2947–2951. [PubMed] [Google Scholar]
  15. Harris D. T., Schumacher M. J., Locascio J., Besencon F. J., Olson G. B., DeLuca D., Shenker L., Bard J., Boyse E. A. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10006–10010. doi: 10.1073/pnas.89.21.10006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hatam L., Schuval S., Bonagura V. R. Flow cytometric analysis of natural killer cell function as a clinical assay. Cytometry. 1994 May 1;16(1):59–68. doi: 10.1002/cyto.990160109. [DOI] [PubMed] [Google Scholar]
  17. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hunt D. W., Huppertz H. I., Jiang H. J., Petty R. E. Studies of human cord blood dendritic cells: evidence for functional immaturity. Blood. 1994 Dec 15;84(12):4333–4343. [PubMed] [Google Scholar]
  19. Keever C. A., Abu-Hajir M., Graf W., McFadden P., Prichard P., O'Brien J., Flomenberg N. Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. Bone Marrow Transplant. 1995 Mar;15(3):407–419. [PubMed] [Google Scholar]
  20. Keever C. A. Characterization of cord blood lymphocyte subpopulations. J Hematother. 1993 Summer;2(2):203–206. doi: 10.1089/scd.1.1993.2.203. [DOI] [PubMed] [Google Scholar]
  21. Krenger W., Ferrara J. L. Dysregulation of cytokines during graft-versus-host disease. J Hematother. 1996 Feb;5(1):3–14. doi: 10.1089/scd.1.1996.5.3. [DOI] [PubMed] [Google Scholar]
  22. Liao N. S., Bix M., Zijlstra M., Jaenisch R., Raulet D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science. 1991 Jul 12;253(5016):199–202. doi: 10.1126/science.1853205. [DOI] [PubMed] [Google Scholar]
  23. Madrigal J. A., Cohen S. B., Gluckman E., Charron D. J. Does cord blood transplantation result in lower graft-versus-host disease? It takes more than two to tango. Hum Immunol. 1997 Aug-Sep;56(1-2):1–5. doi: 10.1016/s0198-8859(97)00125-0. [DOI] [PubMed] [Google Scholar]
  24. Miniero R., Ramenghi U., Crescenzio N., Perugini L., Busca A., Vassallo E., Timeus F. Umbilical cord blood stem cell transplantation. Int J Artif Organs. 1993 Dec;16 (Suppl 5):113–115. [PubMed] [Google Scholar]
  25. Mrózek E., Anderson P., Caligiuri M. A. Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood. 1996 Apr 1;87(7):2632–2640. [PubMed] [Google Scholar]
  26. Quillet A., Presse F., Marchiol-Fournigault C., Harel-Bellan A., Benbunan M., Ploegh H., Fradelizi D. Increased resistance to non-MHC-restricted cytotoxicity related to HLA A, B expression. Direct demonstration using beta 2-microglobulin-transfected Daudi cells. J Immunol. 1988 Jul 1;141(1):17–20. [PubMed] [Google Scholar]
  27. Rabian-Herzog C., Lesage S., Gluckman E. Characterization of lymphocyte subpopulations in cord blood. Bone Marrow Transplant. 1992;9 (Suppl 1):64–67. [PubMed] [Google Scholar]
  28. Rabian-Herzog C., Lesage S., Gluckman E., Charron D. Characterization of lymphocyte subpopulations in cord blood. J Hematother. 1993 Summer;2(2):255–257. doi: 10.1089/scd.1.1993.2.255. [DOI] [PubMed] [Google Scholar]
  29. Rabian-Herzog C., Lesage S., Gluckman E., Charron D. Characterization of lymphocyte subpopulations in cord blood. J Hematother. 1993 Summer;2(2):255–257. doi: 10.1089/scd.1.1993.2.255. [DOI] [PubMed] [Google Scholar]
  30. Robertson M. J., Ritz J. Biology and clinical relevance of human natural killer cells. Blood. 1990 Dec 15;76(12):2421–2438. [PubMed] [Google Scholar]
  31. Suzuki R., Handa K., Itoh K., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). I. Proliferative response and establishment of cloned cells. J Immunol. 1983 Feb;130(2):981–987. [PubMed] [Google Scholar]
  32. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376. doi: 10.1016/S0065-2776(08)60664-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vassiliadou N., Bulmer J. N. Immunohistochemical evidence for increased numbers of 'classic' CD57+ natural killer cells in the endometrium of women suffering spontaneous early pregnancy loss. Hum Reprod. 1996 Jul;11(7):1569–1574. doi: 10.1093/oxfordjournals.humrep.a019439. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES