Immune regulation by non‐lymphoid cells in transplantation

Regulatory cells play a crucial role in the induction and maintenance of tolerance by controlling T cell as well as B and natural killer (NK) cell‐mediated immunity. In transplantation, CD4⁺CD25⁺forkhead box P3⁺ T regulatory cells are instrumental in the maintenance of immunological tolerance, as are several other T cell subsets such as NK T cells, double negative CD3⁺ T cells, γδ T cells, interleukin‐10‐producing regulatory type 1 cells, transforming growth factor‐β‐producing T helper type 3 cells and CD8⁺CD28^‐ cells. However, not only T cells have immunosuppressive properties, as it is becoming increasingly clear that both T and non‐T regulatory cells co‐operate and form a network of cellular interactions controlling immune responses. Non‐T regulatory cells include tolerogenic dendritic cells, plasmacytoid dendritic cells, mesenchymal stem cells, different types of stem cells, various types of alternatively activated macrophages and myeloid‐derived suppressor cells. Here, we review the mechanism of action of these non‐lymphoid regulatory cells as they relate to the induction or maintenance of tolerance in organ transplantation.