Methods for obtaining regulatory t cells and uses thereof
Disclosed is a method for obtaining a population of human Treg cells including the steps of: (a) culturing a population of human monocytes with a medium including an amount of an interleukin-34 (IL-34) polypeptide in order to obtain a population of immunosuppressive macrophages; (b) co-culturing a population of human peripheral blood mononuclear cells (PBMCs) and the population of immunosuppressive macrophages obtained at step (a).
1. A method for treating an immune and/or inflammatory disease or condition in a subject, comprising obtaining a population of human CD8+ CD45RC low Treg cells by: (a) culturing a population of human monocytes in presence of interleukin-34 (IL-34) polypeptide in order to obtain a population of immunosuppressive macrophages; (b) co-culturing a population of human peripheral blood mononuclear cells (PBMCs) and the population of immunosuppressive macrophages obtained at step (a) to obtain a population of human CD8+ CD45RC low Treg cells; and (c) optionally isolating the human CD8+ CD45RC low Treg cells from the population obtained at step (b); and administering said population or said isolated population of human CD8+ CD45RC low Treg cells to the subject, wherein the immune and/or inflammatory disease or condition is selected from the group consisting of an autoimmune disease, graft rejection and GVHD.
2. The method of claim 1 , wherein the population of immunosuppressive macrophages is allogeneic to the population of human PBMCs.
3. The method of claim 1 , wherein the population of human monocytes is a population of CD14+ human monocytes.
4. The method of claim 1 , wherein the IL-34 polypeptide is a human IL-34 polypeptide.
5. The method of claim 1 , wherein the IL-34 polypeptide comprises or consists of SEQ ID NO: 1.
6. The method of claim 1 , wherein the IL-34 polypeptide is added to the culture at a concentration ranging from 1 to 500 ng/mL.
7. The method of claim 1 , wherein the IL-34 polypeptide is added to the culture at a concentration of 50 ng/mL.
8. The method of claim 1 , wherein the co-culture of PBMCs and the population of immunosuppressive macrophages obtained at step (a) is performed in a medium comprising IL-15 and/or IL-2.
9. The method of claim 8 , wherein the cytokines IL-15 and/or IL-2 are human IL-15 and/or human IL-2.
10. The method of claim 1 , wherein the Treg cells are CD8+Foxp3+ CD45RC low Treg cells.
11. The method of claim 1 , wherein the immune and/or inflammatory disease or condition is an autoimmune disease.
12. The method of claim 1 , wherein the immune and/or inflammatory disease or condition is selected from the group consisting of graft rejection and GVHD.