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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10006–10010. doi: 10.1073/pnas.89.21.10006

Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes.

D T Harris 1, M J Schumacher 1, J Locascio 1, F J Besencon 1, G B Olson 1, D DeLuca 1, L Shenker 1, J Bard 1, E A Boyse 1
PMCID: PMC50266  PMID: 1438190

Abstract

Successful implementation of bone marrow transplantation for hematopoietic reconstitution is limited by the lack of suitably HLA-matched donors and by the occurrence of graft-versus-host disease that frequently accompanies this procedure. Recent clinical reports have implied that the use of umbilical cord blood as a source of transplantable stem cells may solve these problems. To date, definitive experiments have not been performed to assess the immunological potential of T cells found in umbilical cord blood, which could mediate graft-versus-host disease. In the present study we have observed that umbilical cord blood contains T lymphocytes that appear to be phenotypically immature. In addition, umbilical cord blood lymphocytes appeared to be functionally immature as shown by minimal responses to stimulation with interleukin 2, phytohemagglutinin, or alloantigens. Thus, umbilical cord blood may be more suitable for allogeneic transplantation than bone marrow in that these cord blood cells may not be as capable of mediating graft-versus-host disease.

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Selected References

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  1. Apperley J. F., Jones L., Hale G., Waldmann H., Hows J., Rombos Y., Tsatalas C., Marcus R. E., Goolden A. W., Gordon-Smith E. C. Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant. 1986 May;1(1):53–66. [PubMed] [Google Scholar]
  2. Atkinson K. Reconstruction of the haemopoietic and immune systems after marrow transplantation. Bone Marrow Transplant. 1990 Apr;5(4):209–226. [PubMed] [Google Scholar]
  3. Brenner C. A., Tam A. W., Nelson P. A., Engleman E. G., Suzuki N., Fry K. E., Larrick J. W. Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells. Biotechniques. 1989 Nov-Dec;7(10):1096–1103. [PubMed] [Google Scholar]
  4. Broxmeyer H. E., Douglas G. W., Hangoc G., Cooper S., Bard J., English D., Arny M., Thomas L., Boyse E. A. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A. 1989 May;86(10):3828–3832. doi: 10.1073/pnas.86.10.3828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broxmeyer H. E., Gluckman E., Auerbach A., Douglas G. W., Friedman H., Cooper S., Hangoc G., Kurtzberg J., Bard J., Boyse E. A. Human umbilical cord blood: a clinically useful source of transplantable hematopoietic stem/progenitor cells. Int J Cell Cloning. 1990 Jan;8 (Suppl 1):76–91. doi: 10.1002/stem.5530080708. [DOI] [PubMed] [Google Scholar]
  6. Foa R., Giubellino M. C., Fierro M. T., Lusso P., Ferrando M. L. Immature T lymphocytes in human cord blood identified by monoclonal antibodies: a model for the study of the differentiation pathway of T cells in humans. Cell Immunol. 1984 Nov;89(1):194–201. doi: 10.1016/0008-8749(84)90209-0. [DOI] [PubMed] [Google Scholar]
  7. Gluckman E., Broxmeyer H. A., Auerbach A. D., Friedman H. S., Douglas G. W., Devergie A., Esperou H., Thierry D., Socie G., Lehn P. Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989 Oct 26;321(17):1174–1178. doi: 10.1056/NEJM198910263211707. [DOI] [PubMed] [Google Scholar]
  8. Granberg C., Hirvonen T. Cell-mediated lympholysis by fetal and neonatal lymphocytes in sheep and man. Cell Immunol. 1980 Apr;51(1):13–22. doi: 10.1016/0008-8749(80)90233-6. [DOI] [PubMed] [Google Scholar]
  9. Granberg C., Manninen K., Toivanen P. Cell-mediated lympholysis by human neonatal lymphocytes. Clin Immunol Immunopathol. 1976 Sep;6(2):256–263. doi: 10.1016/0090-1229(76)90117-3. [DOI] [PubMed] [Google Scholar]
  10. Griffiths-Chu S., Patterson J. A., Berger C. L., Edelson R. L., Chu A. C. Characterization of immature T cell subpopulations in neonatal blood. Blood. 1984 Jul;64(1):296–300. [PubMed] [Google Scholar]
  11. Guidos C. J., Weissman I. L., Adkins B. Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7542–7546. doi: 10.1073/pnas.86.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kolb H. J., Bender-Götze C. Late complications after allogeneic bone marrow transplantation for leukaemia. Bone Marrow Transplant. 1990 Aug;6(2):61–72. [PubMed] [Google Scholar]
  13. Linch D. C., Brent L. Marrow transplantation. Can cord blood be used? Nature. 1989 Aug 31;340(6236):676–676. doi: 10.1038/340676a0. [DOI] [PubMed] [Google Scholar]
  14. Maccario R., Nespoli L., Mingrat G., Vitiello A., Ugazio A. G., Burgio G. R. Lymphocyte subpopulations in the neonate: identification of an immature subset of OKT8-positive, OKT3-negative cells. J Immunol. 1983 Mar;130(3):1129–1131. [PubMed] [Google Scholar]
  15. Noh L. M., Khan M. M., Melmon K. L. Suppressive characteristics of the cultured umbilical cord blood lymphocytes: enhanced suppression of non specific MLR by short term cultured peripheral blood and rosetted lymphocytes. Dev Comp Immunol. 1988 Winter;12(1):177–187. doi: 10.1016/0145-305x(88)90035-3. [DOI] [PubMed] [Google Scholar]
  16. Pross H. F., Baines M. G., Rubin P., Shragge P., Patterson M. S. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol. 1981 Jan;1(1):51–63. doi: 10.1007/BF00915477. [DOI] [PubMed] [Google Scholar]
  17. Ramsdell F., Jenkins M., Dinh Q., Fowlkes B. J. The majority of CD4+8- thymocytes are functionally immature. J Immunol. 1991 Sep 15;147(6):1779–1785. [PubMed] [Google Scholar]
  18. Rayfield L. S., Brent L., Rodeck C. H. Development of cell-mediated lympholysis in human foetal blood lymphocytes. Clin Exp Immunol. 1980 Dec;42(3):561–570. [PMC free article] [PubMed] [Google Scholar]
  19. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Slavin S., Ackerstein A., Naparstek E., Or R., Weiss L. The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? Bone Marrow Transplant. 1990 Sep;6(3):155–161. [PubMed] [Google Scholar]
  21. Witherspoon R. P., Storb R., Ochs H. D., Fluornoy N., Kopecky K. J., Sullivan K. M., Deeg J. H., Sosa R., Noel D. R., Atkinson K. Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment. Blood. 1981 Aug;58(2):360–368. [PubMed] [Google Scholar]
  22. Yeoman H., Mellor A. L. Tolerance and MHC restriction in transgenic mice expressing a MHC class I gene in erythroid cells. Int Immunol. 1992 Jan;4(1):59–65. doi: 10.1093/intimm/4.1.59. [DOI] [PubMed] [Google Scholar]

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