Regulatory B Cell‐Dependent Islet Transplant Tolerance Is Also Natural Killer Cell Dependent. Issue 6 (11th April 2017)

• Record Type: Journal Article
• Authors: Schuetz, C.; Lee, K. M.; Scott, R.; Kojima, L.; Washburn, L.; Liu, L.; Liu, W.‐H.; Tector, H.; Lei, J.; Yeh, H.; Kim, J. I.; Markmann, J. F.
• Is Part Of: American journal of transplantation. Volume 17:Issue 6(2017)
• Page Start: 1656
• Page End: 1662
• Publication Date: 2017-04-11
• Subjects: basic (laboratory) research/science -- islet transplantation -- immunobiology -- tolerance -- natural killer (NK) cells/NK receptors -- B cell biology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14265
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models by using antibodies directed at CD45RB and Tim‐1. We have shown that this form of tolerance depends on regulatory B cells (Bregs). To elucidate further the mechanism by which Bregs induce tolerance, we investigated the requirement of natural killer (NK) and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige, or CD1d − / − mice received BALB/c islet grafts and treatment with the tolerance‐inducing regimen consisting of anti‐CD45RB and anti‐TIM1. B6 mice depleted of both NK and NKT cells by anti‐NK1.1 antibody and mice deficient in NK activity (Beige) did not develop tolerance after dual‐antibody treatment. In contrast, transplant tolerance induction was successful in CD1d − / − recipients (deficient in NKT cells), indicating that NK, but not NKT, cells are essential in B cell–dependent tolerance. In addition, reconstitution of Beige host with NK cells restored the ability to induce transplant tolerance with dual‐antibody treatment. Transfer of tolerance by B cells from tolerant mice was also dependent on host Nk1.1 + cells. In conclusion, these results show that regulatory function of B cells is dependent on NK cells in this model of transplantation tolerance. Abstract : In a model of islet allograft transplant tolerance that depends on Bregs and Tregs for graft survival, the authors determine that tolerance also requires NK cells, suggesting a collaborative interaction of these cell types.