Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire

Bone Marrow Transplantation volume 35, pages 793–801 (2005)Cite this article

Summary:

After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323–339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366–374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Mackall CL, Granger L, Sheard MA et al. T cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived vs thymic-independent progeny. Blood 1993; 82: 2585–2594.

    CAS  Google Scholar 

  2. Avigan D, Pirofski LA, Lazarus HM . Vaccination against infectious disease following hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 171–183.

    Article  CAS  Google Scholar 

  3. Sprent J, Tough DF, Sun S . Factors controlling the turnover of T memory cells. Immunol Rev 1997; 156: 79–85.

    Article  CAS  Google Scholar 

  4. Marrack P, Mitchell T, Bender J et al. T cell survival. Immunol Rev 1998; 165: 279–285.

    Article  CAS  Google Scholar 

  5. Gray D, Matzinger P . T cell memory is short-lived in the absence of antigen. J Exp Med 1991; 174: 969–974.

    Article  CAS  Google Scholar 

  6. Mullbacher A . The long-term maintenance of cytotoxic T cell memory does not require persistence of antigen. J Exp Med 1994; 179: 317–321.

    Article  CAS  Google Scholar 

  7. Lau LL, Jamieson BD, Somasundaram T, Ahmed R . Cytotoxic T cell memory without antigen. Nature 1994; 369: 648–652.

    Article  CAS  Google Scholar 

  8. Sprent J . Immunological memory. Curr Opin Immunol 1997; 9: 371–379.

    Article  CAS  Google Scholar 

  9. Kundig TM, Bachmann MF, Ohashi PS et al. On T cell memory: Arguments for antigen dependence. Immunol Rev 1996; 150: 63–90.

    Article  CAS  Google Scholar 

  10. Anderson LJ, Petropoulos D, Everse LA, Mullen CA . Enhancement of graft-versus-tumor activity and graft-versus-host disease by pretransplant immunization of allogeneic bone marrow donors with a recipient-derived tumor cell vaccine. Cancer Res 1999; 59: 1525–1530.

    CAS  Google Scholar 

  11. Anderson LD, Savary CA, Mullen CA . Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. Blood 2000; 95: 2426–2433.

    CAS  Google Scholar 

  12. Hou S, Hyland L, Ryan KW et al. Virus-specific CD8+ T cell memory determined by clonal burst size. Nature 1994; 369: 652–654.

    Article  CAS  Google Scholar 

  13. Lausen BF, Hougs L, Schejbel L et al. Human memory B cells transferred by allogenic bone marrow transplantation contribute significantly to the antibody repertoire of the recipient. J Immunol 2004; 172: 3305–3318.

    Article  CAS  Google Scholar 

  14. Roux E, Dumont-Girard F, Starobinski M et al. Recovery of immune reactivity after T cell-depleted bone marrow transplantation depends on thymic activity. Blood 2000; 96: 2299–2303.

    CAS  Google Scholar 

  15. Ljungman P, Wiklundhammarsten M, Duraj V et al. Response to tetanus toxoid immunization after allogeneic bone-marrow transplantation. J Infect Dis 1990; 162: 496–500.

    Article  CAS  Google Scholar 

  16. Engelhard D, Handsher R, Naparstek E et al. Immune-response to polio vaccination in bone-marrow transplant recipients. Bone Marrow Transplantat 1991; 8: 295–300.

    CAS  Google Scholar 

  17. Oehen S, Waldner H, Kündig TM et al. Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen. J Exp Med 1992; 176: 1273–1281.

    Article  CAS  Google Scholar 

  18. Anderson LD, Mori S, Mann S et al. Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease. Cancer Res 2000; 60: 5797–5802.

    CAS  Google Scholar 

  19. Redman RL, Nader S, Zerboni L et al. Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine. J Infect Dis 1997; 176: 578–585.

    Article  CAS  Google Scholar 

  20. Davis TA, Hsu FJ, Caspar CB et al. Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma. Biol Blood Marrow Transplant 2001; 7: 517–522.

    Article  CAS  Google Scholar 

  21. Zoller M . Tumor vaccination after allogeneic bone marrow cell reconstitution of the nonmyeloablatively conditioned tumor-bearing murine host. J Immunol 2003; 171: 6941–6953.

    Article  Google Scholar 

  22. Borrello I, Sotomayor EM, Rattis FM et al. Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte–macrophage colony-stimulating factor (GM-CSF)-producing tumor vaccines. Blood 2000; 95: 3011–3019.

    CAS  Google Scholar 

  23. Ochsenbein AF, Klenerman P, Karrer U et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci USA 1999; 96: 2233–2238.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Research Scholar Grant (RSG-98-035-04-LIB) from the American Cancer Society (CAM) and grant support from the National Institutes of Health (5T32CA073954-05) (SM) (1 R01 CA10628-01) (CAM). We are grateful to Dr Cherylyn Savary for her generous assistance with flow cytometry.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Rochester Medical Center, Rochester, NY, USA

    S Mori & C A Mullen

  2. Department of Pediatrics, Kýrýkkale University Medical Faculty, Kirikkale, Turkey

    U Kocak

  3. Department of Immunology, MD Anderson Cancer Center, Houston, TX, USA

    J L Shaw

Authors
  1. S Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U Kocak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J L Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C A Mullen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C A Mullen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mori, S., Kocak, U., Shaw, J. et al. Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire. Bone Marrow Transplant 35, 793–801 (2005). https://doi.org/10.1038/sj.bmt.1704883

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704883

Keywords

This article is cited by

Search

Advanced search

Quick links