Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells

Haspot, F., Li, H. W., Lucas, C. L., Fehr, T., Beyaz, S., Sykes, M. (January 2014) Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells. Am J Transplant, 14 (1). pp. 49-58. ISSN 1600-6143 (Electronic)1600-6135 (Linking)

DOI: 10.1111/ajt.12525


Avoidance of long-term immunosuppression is a desired goal in organ transplantation. Mixed chimerism offers a promising approach to tolerance induction, and we have aimed to develop low-toxicity, nonimmunodepleting approaches to achieve this outcome. In a mouse model achieving fully MHC-mismatched allogeneic bone marrow engraftment with minimal conditioning (3 Gy total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone marrow cells), CD4 T cells in the recipient are required to promote tolerance of preexisting alloreactive recipient CD8 T cells and thereby permit chimerism induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject MHC Class I-deficient and Class I/Class II-deficient marrow in a CD8 T cell-dependent manner. This rejection is specific for donor alloantigens, since recipient hematopoiesis is not affected by donor marrow rejection and MHC Class I-deficient bone marrow that is syngeneic to the recipient is not rejected. Recipient CD8 T cells are activated and develop cytotoxicity against MHC Class I-deficient donor cells in association with rejection. These data implicate a novel CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells indirectly activated by donor alloantigens promote direct killing, in a T cell receptor-independent manner, of Class I-deficient donor cells.

Item Type: Paper
Uncontrolled Keywords: Animals Bone Marrow/immunology *Bone Marrow Transplantation CD8-Positive T-Lymphocytes/*immunology H-2 Antigens/*immunology Immune Tolerance/immunology Isoantigens/*immunology Mice Transplantation Chimera Transplantation Conditioning *Transplantation, Homologous Transplantation, Isogeneic Bone marrow transplantation CD8 T cells indirect alloreactivity tolerance
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > bone marrow
therapies > bone marrow transplantation
CSHL Authors:
Communities: CSHL labs > Beyaz lab
Depositing User: Matt Covey
Date: January 2014
Date Deposited: 02 Feb 2018 17:56
Last Modified: 02 Feb 2018 17:56
PMCID: PMC4045013
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