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The mononuclear phagocyte system (MPS) comprises monocytes, macrophages and dendritic cells (DCs). Over the past few decades, classification of the cells of the MPS has generated considerable controversy. Recent studies into the origin, developmental requirements and function of MPS cells are beginning to solve this problem in an objective manner. Using high-resolution genetic analyses and fate-mapping studies, three main mononuclear phagocyte lineages have been defined, namely, macrophage populations established during embryogenesis, monocyte-derived cells that develop during adult life and DCs. These subsets and their diverse subsets have specialized functions that are largely conserved between species, justifying the introduction of a new, universal scheme of nomenclature and providing the framework for therapeutic manipulation of immune responses in the clinic. In this review, we have commented on the implications of this novel MPS classification in solid organ transplantation.

The mononuclear phagocyte system (MPS) comprises monocytes, macrophages and dendritic cells (DCs). Over the past few decades, classification of the cells of the MPShas generated considerable controversy. Recent studies into the origin, developmental requirements and function of MPScells are beginning to solve this problem in an objective manner. Using high‐resolution genetic analyses and fate‐mapping studies, three main mononuclear phagocyte lineages have been defined, namely, macrophage populations established during embryogenesis, monocyte‐derived cells that develop during adult life and DCs. These subsets and their diverse subsets have specialized functions that are largely conserved between species, justifying the introduction of a new, universal scheme of nomenclature and providing the framework for therapeutic manipulation of immune responses in the clinic. In this review, we have commented on the implications of this novel MPSclassification in solid organ transplantation. The authors review the implications of a novel mononuclear phagocyte system nomenclature in solid organ transplantation and provide the phenotypic characterization to distinguish its multiple subsets.

Myeloid-derived suppressor cells (MDSC) are negative regulators of the immune response and are in part responsible for the inhibition of the T cell–mediated immune responses. While MDSC have been demonstrated to participate in the induction of prolonged allograft survival in animal models of transplantation, little is known about their immune regulatory function in human transplant recipients. Here, we report that two subsets of human MDSC expressing CD11b+, CD33+and HLA-DR−develop in renal patients posttransplantation. We found that CD14+expressing monocytic MDSC isolated from transplant recipients were highly efficient in suppressing the proliferation of CD4+T cells in mixed leukocyte reactions. In addition, we observed that CD11b+CD33+HLA-DR−MDSC are capable of expanding Treg in vitro, and their accumulation overtime after transplantation linearly correlated with an increase in Treg in vivo. This is the first study to link the presence of MDSC with the emergence of Treg in vivoin transplant recipients, and to define the subpopulation of MDSC derived from transplant recipients responsible for generation of Treg. Further studies are necessary to determine the alloimmune regulatory function of MDSC in human transplant recipients.

The authors demonstrate that myeloid‐derived suppressor cells are increased in renal transplant recipients, and they delineate the population of myeloid cells responsible with the emergence of regulatory T cells and the suppression of the alloimmune response in humans. See editorial by Thomson and Turnquist on page 3061.

Interactions of donor and recipient dendritic cells (DCs) with CD4+ T cells determine the alloantigenic response in organ transplantation, where recipient T cells respond either directly to donor MHC, or indirectly to processed donor MHC allopeptides in the context of recipient MHC molecules. The present study evaluates donor and recipient alloantigen-presenting DC trafficking and their interactions with CD4+ T cells in the lymph nodes (LNs) and the spleen under tolerogenic treatment with anti-CD2 plus anti-CD3 mAb compared with untreated rejecting conditions. CX3CR1GFP BALB/c (I-Ad) donor hearts were transplanted into C57BL/6 (I-Ab) mice and quantification of donor DC direct (GFP+ or I-Ad+) and recipient DC indirect (YAe+) trafficking and interactions with host CD4+ T cells was performed by fluorescent microscopy. Our data indicate that although both direct and indirect interactions between CD4+ T cells and donor and recipient DCs occur shortly after engraftment, only indirect presentation persists in the LN, but not the spleen, of tolerized recipients. These data suggest that distinct anatomic lymphoid compartments play a critical role in peripheral tolerance induction and maintenance, and persistent indirect presentation to CD4+ T cells within the LNs is an important process during tolerization.

This editorial provides commentary on Hongo et al's (page 2467) demonstration that transplant tolerance induction after recipient conditioning with total lymphoid irradiation, antithymocyte serum, and donor bone marrow transplantation requires arginase‐1–expressing myeloid‐derived suppressor cells that are generated in response to invariant natural killer T cell interleukin‐4 production.

Discussion on the manipulation of myeloid suppressor cells as a novel therapeutic approach in organ transplantation.