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Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients.
J Immunol. 2001 Mar 01; 166(5):3174-83.JI

Abstract

4-1BB is expressed on activated CD4(+) and CD8(+) T cells; its ligand, 4-1BB ligand is expressed on APCs. Despite expression on both T cell subpopulations, 4-1BB has been reported to predominantly affect CD8(+) T cell responses. By quantifying graft-vs-host disease alloresponses in vivo, we demonstrate that both CD4(+) and CD8(+) T cell-mediated alloresponses are regulated by 4-1BB/4-1BB ligand interactions to approximately the same extent. 4-1BB receptor-facilitated CD4(+) T cell-mediated alloresponses were partly CD28 independent. In two distinct marrow graft rejection systems, host CD8(+) and CD4(+) T cells each separately contributed to host anti-donor T cell-mediated allograft rejection. alpha 4-1BB mAb increased the graft-vs-leukemia effect of a suboptimal number of donor splenocytes given later post bone marrow transplantation by bolstering allogeneic responses resulting in leukemia elimination. In summary, 4-1BB ligation is a potent regulator of CD4(+) and CD8(+) T cell-mediated allogeneic responses in vivo. Modifying the ligation of 4-1BB represents a new approach to altering the graft-vs-host disease and graft-vs-leukemia effects of allogeneic T cells post bone marrow transplantation.

Authors+Show Affiliations

University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN 55455, USA. blaza001@tc.umn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11207270

Citation

Blazar, B R., et al. "Ligation of 4-1BB (CDw137) Regulates Graft-versus-host Disease, Graft-versus-leukemia, and Graft Rejection in Allogeneic Bone Marrow Transplant Recipients." Journal of Immunology (Baltimore, Md. : 1950), vol. 166, no. 5, 2001, pp. 3174-83.
Blazar BR, Kwon BS, Panoskaltsis-Mortari A, et al. Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. J Immunol. 2001;166(5):3174-83.
Blazar, B. R., Kwon, B. S., Panoskaltsis-Mortari, A., Kwak, K. B., Peschon, J. J., & Taylor, P. A. (2001). Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. Journal of Immunology (Baltimore, Md. : 1950), 166(5), 3174-83.
Blazar BR, et al. Ligation of 4-1BB (CDw137) Regulates Graft-versus-host Disease, Graft-versus-leukemia, and Graft Rejection in Allogeneic Bone Marrow Transplant Recipients. J Immunol. 2001 Mar 1;166(5):3174-83. PubMed PMID: 11207270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft-versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. AU - Blazar,B R, AU - Kwon,B S, AU - Panoskaltsis-Mortari,A, AU - Kwak,K B, AU - Peschon,J J, AU - Taylor,P A, PY - 2001/2/24/pubmed PY - 2001/5/1/medline PY - 2001/2/24/entrez SP - 3174 EP - 83 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 166 IS - 5 N2 - 4-1BB is expressed on activated CD4(+) and CD8(+) T cells; its ligand, 4-1BB ligand is expressed on APCs. Despite expression on both T cell subpopulations, 4-1BB has been reported to predominantly affect CD8(+) T cell responses. By quantifying graft-vs-host disease alloresponses in vivo, we demonstrate that both CD4(+) and CD8(+) T cell-mediated alloresponses are regulated by 4-1BB/4-1BB ligand interactions to approximately the same extent. 4-1BB receptor-facilitated CD4(+) T cell-mediated alloresponses were partly CD28 independent. In two distinct marrow graft rejection systems, host CD8(+) and CD4(+) T cells each separately contributed to host anti-donor T cell-mediated allograft rejection. alpha 4-1BB mAb increased the graft-vs-leukemia effect of a suboptimal number of donor splenocytes given later post bone marrow transplantation by bolstering allogeneic responses resulting in leukemia elimination. In summary, 4-1BB ligation is a potent regulator of CD4(+) and CD8(+) T cell-mediated allogeneic responses in vivo. Modifying the ligation of 4-1BB represents a new approach to altering the graft-vs-host disease and graft-vs-leukemia effects of allogeneic T cells post bone marrow transplantation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11207270/Ligation_of_4_1BB__CDw137__regulates_graft_versus_host_disease_graft_versus_leukemia_and_graft_rejection_in_allogeneic_bone_marrow_transplant_recipients_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11207270 DB - PRIME DP - Unbound Medicine ER -