Compositions and methods for generating interleukin-35-induced regulatory t cells
AssigneeSt. Jude Children's Research Hospital
InventorsDario AA Vignali, Lauren W. Collison
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Abstract
Compositions and methods are provided for generating T cells having a regulatory phenotype from conventional T (Tconv) cells. Such compositions and methods include culturing isolated, naïve Tconv cells with an effective amount of interleukin-35 (IL-35) until the cells have the regulatory phenotype. Also provided are methods to treat subject having or susceptible to having various disorders including, for example, immune system disorders with the T cells having the regulatory phenotype.
Claims46
An isolated population of IL-35 induced Treg (iTr35) cells wherein said iTr35 cells have the following characteristics:
- a) express intrinsic IL-35 wherein EBI3 and p35 express at levels higher than that found in a Tconv cell population;
- b) Foxp3 is not expressed at a physiologically relevant level;
- c) have anergy;
- and,
- d) suppress the proliferation of naïve conventional T (Tconv) cells.
A method of generating a population of IL-35 induced Treg (iTr35) cells comprising activating in-vitro or ex vivo an isolated population of conventional T (Tconv) cells and culturing said activated cell population with an effective amount of an exogenous form of Interleukin-35 (IL-35) and thereby inducing the conversion of the Tconv cells to the iTr35 cells, wherein said iTr35 cells are characterized by:
- a) Expressing intrinsic IL-35 wherein EBI3 and p35 at levels higher than that found in a Tconv cell population;
- b) Foxp3 is not expressed at a physiologically relevant level;
- c) have anergy;
- and,
- d) suppress the proliferation of naïve Tconv cells.
A method to treat an immune system disorder, the method comprising:
- a) activating in vitro an isolated population of conventional T (Tconv) cells from a subject having or suspected of having an immune system disorder and culturing said activated population with an effective amount of exogenous Interleukin-35 (IL-35) and thereby inducing the conversion of the Tconv cells to a iTr35 cells, wherein said iTr35 cells are characterized by:
- i) expressing native EBI3 and p35 at levels higher than that found in a Tconv cell population;
- ii) Foxp3 is not expressed at a physiologically relevant level;
- iii) have anergy;
- and,
- iv) suppress the proliferation of naïve Tconv cells;
- b) administering to the subject a therapeutically effective amount of the iTr35 cells to treat the immune system disorder.
Dependencies are inferred from the claim text.