Humoral immunity is the dominant barrier for allogeneic bone marrow engraftment in sensitized recipients
Open Access
- 15 November 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (10), 3611-3619
- https://doi.org/10.1182/blood-2006-04-017467
Abstract
We evaluated the relative contribution of the humoral and cellular arms of the immune response to bone marrow cells transplanted into sensitized recipients. We report here for the first time that humoral immunity contributes predominantly to allosensitization. Although the major role for nonmyeloablative conditioning is to control alloreactive host T cells in nonsensitized recipients, strikingly, none of the strategies directed primarily at T-cell alloreactivity enhanced engraftment in sensitized mice. In evaluating the mechanism behind this barrier, we found that humoral immunity plays a critical role in the rejection of allogeneic marrow in sensitized recipients. Adoptive transfer of as little as 25 μL serum from sensitized mice abrogated engraftment in secondary naive recipients. With the use of μMT mice as recipients, we found that T-cell-mediated immunity plays a secondary but still significant role in allorejection. Targeting of T cells in sensitized B-cell-deficient μMT mice enhanced alloengraftment. Moreover, both T- and B-cell tolerance were achieved in sensitized recipients when allochimerism was established, as evidenced by the acceptance of second donor skin grafts and loss of circulating donor-specific Abs. These findings have important implications for the management of sensitized transplant recipients and for xenotransplantation in which B-cell reactivity is a predominant barrier.Keywords
This publication has 36 references indexed in Scilit:
- Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft FunctionAmerican Journal of Transplantation, 2005
- THE B7 FAMILY REVISITEDAnnual Review of Immunology, 2005
- Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftmentBlood, 2004
- Tolerization of Galα1,3Gal‐reactive B cells in pre‐sensitized α1,3‐galactosyltransferase‐deficient mice by nonmyeloablative induction of mixed chimerismXenotransplantation, 2001
- Self‐renewal of B‐1 lymphocytes is dependent on CD19European Journal of Immunology, 1996
- Therapeutic plasmapheresisCurrent Opinion in Hematology, 1996
- RENAL TRANSPLANTATION FOLLOWING IMMUNOADSORPTION IN HIGHLY SENSITIZED RECIPIENTSTransplantation, 1993
- The effect of panel reactive antibodies and the donor specific crossmatch on graft survival after heart and heart-lung transplantationTransplant Immunology, 1993
- Laboratory and clinical management of the highly sensitized organ transplant recipientHuman Immunology, 1989
- THE FLOW CYTOMETRIC CROSSMATCHTransplantation, 1989