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. 1995 Mar 14;92(6):2413–2417. doi: 10.1073/pnas.92.6.2413

Alloantigen priming induces a state of unresponsiveness in human umbilical cord blood T cells.

G Risdon 1, J Gaddy 1, M Horie 1, H E Broxmeyer 1
PMCID: PMC42494  PMID: 7892281

Abstract

Induction of alloreactivity in human adult and umbilical cord blood T cells was evaluated in mixed leukocyte culture by exposure to an allogeneic lymphoblastoid line that expresses known costimulatory molecules. Initial exposure to alloantigen-presenting cells (allo-APC) induced strong proliferative responses in both adult and cord blood T cells. However, in contrast to adult T cells, cord blood T cells exhibited little proliferation after restimulation with donor APC. Primed cord blood T cells could respond to interleukin 2 (IL-2), but unresponsiveness to alloantigen was not overcome by addition of exogenous IL-2. Unresponsiveness was long-lasting and appeared to be maintained by a combination of induction of anergy and activity of CD8+ suppressor cells. This information may contribute to use of human cord blood as an allogeneic source of transplantable stem cells.

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Selected References

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

  1. Anasetti C., Tan P., Hansen J. A., Martin P. J. Induction of specific nonresponsiveness in unprimed human T cells by anti-CD3 antibody and alloantigen. J Exp Med. 1990 Dec 1;172(6):1691–1700. doi: 10.1084/jem.172.6.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azuma M., Cayabyab M., Buck D., Phillips J. H., Lanier L. L. CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med. 1992 Feb 1;175(2):353–360. doi: 10.1084/jem.175.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azuma M., Ito D., Yagita H., Okumura K., Phillips J. H., Lanier L. L., Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993 Nov 4;366(6450):76–79. doi: 10.1038/366076a0. [DOI] [PubMed] [Google Scholar]
  4. Azuma M., Phillips J. H., Lanier L. L. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993 Feb 15;150(4):1147–1159. [PubMed] [Google Scholar]
  5. Bogdanić V., Nemet D., Kastelan A., Latin V., Petrovecki M., Brkljacić-Surlaković L., Kerhin-Brkljacić V., Aurer I., Konja J., Mrsić M. Umbilical cord blood transplantation in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Transplantation. 1993 Aug;56(2):477–479. [PubMed] [Google Scholar]
  6. Boussiotis V. A., Freeman G. J., Gray G., Gribben J., Nadler L. M. B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance. J Exp Med. 1993 Nov 1;178(5):1753–1763. doi: 10.1084/jem.178.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Broxmeyer H. E., Kurtzberg J., Gluckman E., Auerbach A. D., Douglas G., Cooper S., Falkenburg J. H., Bard J., Boyse E. A. Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation. Blood Cells. 1991;17(2):313–329. [PubMed] [Google Scholar]
  9. Ehlers S., Smith K. A. Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med. 1991 Jan 1;173(1):25–36. doi: 10.1084/jem.173.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freeman G. J., Gribben J. G., Boussiotis V. A., Ng J. W., Restivo V. A., Jr, Lombard L. A., Gray G. S., Nadler L. M. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993 Nov 5;262(5135):909–911. doi: 10.1126/science.7694363. [DOI] [PubMed] [Google Scholar]
  11. Gerli R., Agea E., Muscat C., Tognellini R., Fiorucci G., Spinozzi F., Cernetti C., Bertotto A. Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response. Cell Immunol. 1993 Apr 15;148(1):32–47. doi: 10.1006/cimm.1993.1089. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kohli-Kumar M., Shahidi N. T., Broxmeyer H. E., Masterson M., Delaat C., Sambrano J., Morris C., Auerbach A. D., Harris R. E. Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLA-matched sibling umbilical cord blood cells. Br J Haematol. 1993 Oct;85(2):419–422. doi: 10.1111/j.1365-2141.1993.tb03192.x. [DOI] [PubMed] [Google Scholar]
  14. Kurtzberg J., Graham M., Casey J., Olson J., Stevens C. E., Rubinstein P. The use of umbilical cord blood in mismatched related and unrelated hemopoietic stem cell transplantation. Blood Cells. 1994;20(2-3):275–284. [PubMed] [Google Scholar]
  15. Merkenschlager M., Ikeda H., Wilkinson D., Beverly P. C., Trowsdale J., Fisher A. G., Altmann D. M. Allorecognition of HLA-DR and -DQ transfectants by human CD45RA and CD45R0 CD4 T cells: repertoire analysis and activation requirements. Eur J Immunol. 1991 Jan;21(1):79–88. doi: 10.1002/eji.1830210113. [DOI] [PubMed] [Google Scholar]
  16. Risdon G., Gaddy J., Stehman F. B., Broxmeyer H. E. Proliferative and cytotoxic responses of human cord blood T lymphocytes following allogeneic stimulation. Cell Immunol. 1994 Mar;154(1):14–24. doi: 10.1006/cimm.1994.1053. [DOI] [PubMed] [Google Scholar]
  17. Tan P., Anasetti C., Hansen J. A., Melrose J., Brunvand M., Bradshaw J., Ledbetter J. A., Linsley P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993 Jan 1;177(1):165–173. doi: 10.1084/jem.177.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tan P., Anasetti C., Martin P. J., Hansen J. A. Alloantigen-specific T suppressor-inducer and T suppressor-effector cells can be activated despite blocking the IL-2 receptor. J Immunol. 1990 Jul 15;145(2):485–488. [PubMed] [Google Scholar]
  19. Van Gool S. W., Ceuppens J. L., Walter H., de Boer M. Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking alloantigen-induced T-cell activation. Blood. 1994 Jan 1;83(1):176–183. [PubMed] [Google Scholar]
  20. Van Gool S. W., de Boer M., Ceuppens J. L. The combination of anti-B7 monoclonal antibody and cyclosporin A induces alloantigen-specific anergy during a primary mixed lymphocyte reaction. J Exp Med. 1994 Feb 1;179(2):715–720. doi: 10.1084/jem.179.2.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vilmer E., Sterkers G., Rahimy C., Denamur E., Elion J., Broyart A., Lescoeur B., Tiercy J. M., Gerota J., Blot P. HLA-mismatched cord-blood transplantation in a patient with advanced leukemia. Transplantation. 1992 May;53(5):1155–1157. [PubMed] [Google Scholar]
  22. Vowels M. R., Tang R. L., Berdoukas V., Ford D., Thierry D., Purtilo D., Gluckman E. Brief report: correction of X-linked lymphoproliferative disease by transplantation of cord-blood stem cells. N Engl J Med. 1993 Nov 25;329(22):1623–1625. doi: 10.1056/NEJM199311253292205. [DOI] [PubMed] [Google Scholar]
  23. Wagner J. E., Broxmeyer H. E., Byrd R. L., Zehnbauer B., Schmeckpeper B., Shah N., Griffin C., Emanuel P. D., Zuckerman K. S., Cooper S. Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. Blood. 1992 Apr 1;79(7):1874–1881. [PubMed] [Google Scholar]
  24. Wagner J. E. Umbilical cord blood transplantation: overview of the clinical experience. Blood Cells. 1994;20(2-3):227–234. [PubMed] [Google Scholar]
  25. Zanders E. D., Lamb J. R., Feldmann M., Green N., Beverley P. C. Tolerance of T-cell clones is associated with membrane antigen changes. Nature. 1983 Jun 16;303(5918):625–627. doi: 10.1038/303625a0. [DOI] [PubMed] [Google Scholar]

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