Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation

Leonard J. Appleman, Dimitrios Tzachanis, Thomas Grader Beck, Andre A F L Van Puijenbroek, Vassiliki A. Boussiotis

Research output: Contribution to journalArticle

Abstract

The ability to achieve complete hematopoietic engraftment in the allogeneic setting without intensive myeloablative chemotherapy will have a profound effect on the practice of allogeneic hematopoietic cell transplantation (HCT). Novel methods to induce antigen-specific T-cell tolerance provide promise to ensure engraftment and reduce GVHD without producing generalized and other toxicities caused by myeloablative conditioning regimens. Compelling experimental evidence indicates that the antigen receptors on T-lymphocytes have dual potential to transmit crucial activation signals for initiating immune responses and to discharge equally potent inactivating signals to abort or inhibit immune responses. Many events impact on this fundamental decision-making process and one of the great challenges for modern immunology is to decipher the molecular wiring that integrates and converts the extrinsic and intrinsic variables into positive or negative cellular responses termed immunity and anergy, respectively. Our currently expanding understanding of the biochemical and molecular basis of T-cell anergy provides great promise to improve our ability to design novel clinical therapeutic approaches in order to induce antigen-specific tolerance in vivo. Importantly, strategies now exist to segregate graft versus tumor (GVT) effects from GVHD. Therefore, achievement of limited and specific tolerance to host alloantigens by selectively inactivating the indicated subsets of alloantigen-specific T-lymphocytes will prevent GVHD but retain the GVT effect of the graft. Such treatment approaches will expand the donor pool, because they will allow transplantation between individuals with increasing human leukocyte antigen (HLA) disparity, enable reduction of the need for non-specific immunosuppression, and reduce the risk of opportunistic infections and relapse of leukemia.

Original languageEnglish (US)
Pages (from-to)1159-1167
Number of pages9
JournalLeukemia and Lymphoma
Volume43
Issue number6
StatePublished - 2002
Externally publishedYes

Fingerprint

Cell Transplantation
T-Lymphocytes
Aptitude
Isoantigens
Transplants
Antigens
Antigen Receptors
Opportunistic Infections
HLA Antigens
Allergy and Immunology
Immunosuppression
Immunity
Neoplasms
Decision Making
Leukemia
Transplantation
Recurrence
Drug Therapy
Therapeutics

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Chemotherapy
  • Immunologic tolerance
  • Immunosuppression

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Appleman, L. J., Tzachanis, D., Grader Beck, T., Van Puijenbroek, A. A. F. L., & Boussiotis, V. A. (2002). Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation. Leukemia and Lymphoma, 43(6), 1159-1167.

Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation. / Appleman, Leonard J.; Tzachanis, Dimitrios; Grader Beck, Thomas; Van Puijenbroek, Andre A F L; Boussiotis, Vassiliki A.

In: Leukemia and Lymphoma, Vol. 43, No. 6, 2002, p. 1159-1167.

Research output: Contribution to journalArticle

Appleman, LJ, Tzachanis, D, Grader Beck, T, Van Puijenbroek, AAFL & Boussiotis, VA 2002, 'Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation', Leukemia and Lymphoma, vol. 43, no. 6, pp. 1159-1167.
Appleman LJ, Tzachanis D, Grader Beck T, Van Puijenbroek AAFL, Boussiotis VA. Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation. Leukemia and Lymphoma. 2002;43(6):1159-1167.
Appleman, Leonard J. ; Tzachanis, Dimitrios ; Grader Beck, Thomas ; Van Puijenbroek, Andre A F L ; Boussiotis, Vassiliki A. / Induction of immunologic tolerance for allogeneic hematopoietic cell transplantation. In: Leukemia and Lymphoma. 2002 ; Vol. 43, No. 6. pp. 1159-1167.
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