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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Anti-CD45RB/anti-TIM-1-induced tolerance requires regulatory B cells
1Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Regulatory B cells promote transplant tolerance via an IL-10-dependent pathway. Combining anti-CD45RB and anti-TIM-1 antibodies induces long-term islet graft survival in mice, highlighting a novel B-cell role in transplantation.
Area of Science:
- Immunology
- Transplantation Biology
- Cellular and Molecular Medicine
Background:
- The precise role of B cells in transplant tolerance is not fully understood.
- B-cell depletion can inconsistently affect graft survival, suggesting a potential regulatory function.
- Previous research indicated B cells are necessary for tolerance induction by anti-CD45RB therapy.
Purpose of the Study:
- To investigate the synergistic effect of anti-CD45RB and anti-TIM-1 antibodies on transplant tolerance.
- To elucidate the role of B cells and Interleukin-10 (IL-10) in this tolerance induction model.
Main Methods:
- Utilized a mouse islet allograft model.
- Administered combined anti-CD45RB and anti-TIM-1 antibody therapy.
- Assessed graft survival and analyzed the dependence on recipient B cells and B-cell IL-10 activity.
Main Results:
- The combination of anti-CD45RB and anti-TIM-1 antibodies induced synergistic tolerance, leading to complete graft acceptance in all recipients.
- This tolerance was dependent on the presence of recipient B cells.
- B-cell-derived IL-10 activity was essential for the observed tolerance.
- The tolerance induced was antigen-specific.
Conclusions:
- A regulatory B-cell population exists that promotes transplant tolerance.
- This regulatory activity is mediated through an IL-10-dependent pathway.
- Combined antibody blockade targeting CD45RB and TIM-1 offers a promising strategy for inducing antigen-specific transplant tolerance.
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