Differentiation of MUTZ-3 cells to produce effective dendritic cells
Disclosed is a method for the production and use of CD124+ and CD116+ cell lines in the production of effective dendritic cells (DC) with the aid of stimulatory molecules.
1. A method for the production of non-proliferating immature dendritic cells, comprising
(i) contacting MUTZ- 3 cells with
(a) GM-CSF, TNFα, and IL- 4 ; or
(b) GM-CSF and TNF-α followed by TGFβ 1 ; and
(ii) obtaining the non-proliferating immature dendritic cells through differentiation of the contacted MUTZ- 3 cells.
2. The method according to claim 1 , further comprising contacting the non-proliferating immature dendritic cells with
(a) TNFα;
(b) LPS;
(c) CD 40 ligand; or
(d) polyinosinic-polycytidylic acid (polyIC)
to produce mature dendritic cells.
3. The method according to claim 1 , further comprising contacting the immature dendritic cells with TNFα and IFNγ to produce type 1 dendritic cells (DC type 1).
4. The method according to claim 1 , further comprising contacting the immature dendritic cells with TNFα and dexamethasone to produce type 2 dendritic cells (DC type 2).
5. The method according to claim 1 , wherein the MUTZ-3 cells are CD34-positive.
6. The method according to claim 5 , wherein a gene for CD34 is introduced into the MUTZ-3 cells.
7. The method according to claim 1 , further comprising introducing an antigen encoding gene into the dendritic cells.
8. The method according to claim 1 , wherein the dendritic cells are fused with other cells or cell lines.
9. The method according to claim 1 , further comprising exposing the non-proliferating immature dendritic cells to a treatment causing the non-proliferating immature dendritic cells to undergo apoptosis or necrosis.
10. The method according to claim 8 , wherein said treatment is selected from the group consisting of irradiation, thermal shock, mechanical stress, oxidative stress, ultrasound, induction of suicide genes and induction with a chemical or biological molecule selected from the group consisting of glycerol, zinc, butilinic acid, sodium butyrate, leptomycin B with ST1571 and Fas ligand.
11. A method for the production of non-proliferating immature dendritic cells, comprising
(i) contacting MUTZ- 3 cells with GM-CSF, TNFα, and IL- 13 ; and
(ii) obtaining the non-proliferating immature dendritic cells through differentiation of the contacted MUTZ- 3 cells.
12. The method according to claim 11 , further comprising contacting the non-proliferating immature dendritic cells with
(a) TNFα;
(b) LPS;
(c) CD 40 ligand; or
(d) polyinosinic-polycytidylic acid (polyIC)
to produce mature dendritic cells.
13. The method according to any one of claims 1 , 2 , 4 , or 11 , wherein the dendritic cells are used for treatment of a disease selected from the group consisting of infectious diseases and tumor diseases.