Methods of activating nkt cells

Abstract

Provided are methods of activating an NKT cell which include a step of contacting the NKT cell with a sufficient amount of isoglobotrihexosylceramide (iGb3) to induce secretion of a cytokine from the NKT cell, stimulate proliferation of the NKT cell or upregulate expression of a cell surface marker on the NKT cell. Methods of activating an NKT cell population in a subject are also provided.

1 . A method of activating an NKT cell comprising contacting the NKT cell with a sufficient amount of iGb3 to induce secretion of a cytokine from the NKT cell, stimulate proliferation of the NKT cell or upregulate expression of a cell surface marker on the NKT cell, wherein contacting the NKT cell comprises administering iGb3 or an iGb3 precursor to a subject comprising the NKT cell. 
     
     
         2 . The method of  claim 1 , wherein the iGb3 is purified or synthetic. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the iGb3 is presented to the NKT cell by an antigen presenting cell comprising a CD1d molecule. 
     
     
         6 . The method of  claim 5 , wherein the antigen presenting cell is a dendritic cell. 
     
     
         7 . The method of  claim 5 , wherein the iGb3 precursor is provided to the antigen presenting cell to produce the iGb3. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         12 . The method of  claim 11 , wherein the mammal is a human. 
     
     
         13 . The method of  claim 1 , wherein the cytokine is selected from the group consisting of IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, TNF-α, TNF-β, IFN-γ and combinations thereof. 
     
     
         14 . The method of  claim 13 , wherein the cytokine is IFN-γ, IL-2, or IL-4. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the cell surface marker is CD69, CD25, an IL-12 receptor or CD40L. 
     
     
         18 . A method of activating an NKT cell in a subject comprising administering iGb3 or an iGb3 precursor to the subject in an amount sufficient to induce secretion of a cytokine from the NKT cell, stimulate proliferation of the NKT cell or upregulate expression of a cell surface marker on the NKT cell. 
     
     
         19 . The method of  claim 18 , wherein the iGb3 or iGb3 precursor is purified or synthetic. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 19 , wherein the precursor is iGb4. 
     
     
         22 . The method of  claim 18 , wherein the subject has cancer, an autoimmune disorder, or an infection. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 18 , wherein the cytokine is selected from the group consisting of IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, TNF-α, TNF-β, IFN-γ and combinations thereof. 
     
     
         26 . The method of  claim 25 , wherein the cytokine is IFN-γ, IL-2, or IL-4. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 18 , wherein the cell surface marker is an IL-12 receptor or CD40L. 
     
     
         30 . A method of inducing secretion of a cytokine from an NKT cell comprising contacting the NKT cell with iGb3. 
     
     
         31 . A method of stimulating proliferation of an NKT cell comprising contacting the NKT cell with iGb3. 
     
     
         32 . A method of upregulating expression of a cell surface marker on an NKT cell comprising contacting the NKT cell with iGb3.