Materials and methods for modifying the activity of t cells

Abstract

This disclosure provides miRNA/mRNA pairs that can be used to increase the efficacy of T cells or to down-modulate T cell efficacy and restore equilibrium.

1 . A method of increasing the survival, stability and/or function of T cells, comprising:
 providing T cells from an individual;   contacting the T cells with at least one moiety that decreases or inhibits miRNA-146b, miRNA-4484 or miRNA-155; and   introducing the contacted T cells back into the individual.   
     
     
         2 . The method of  claim 1 , wherein the at least one moiety is selected from the group consisting of a nucleic acid molecule, a small molecule, a polypeptide, and an anti-miR. 
     
     
         3 . The method of  claim 2 , wherein the nucleic acid molecule is a RNA interference molecule. 
     
     
         4 . The method of  claim 2 , wherein the polypeptide is an antibody. 
     
     
         5 . The method of  claim 2 , wherein the anti-miR is an antagomir. 
     
     
         6 . The method of  claim 1 , wherein the T cells are contacted with the moiety on day 0. 
     
     
         7 . The method of  claim 1 , wherein the T cells are cultured for about 1 to about 21 days before being contacted with the moiety. 
     
     
         8 . The method of  claim 1 , wherein the T cells are contacted with the moiety for several hours to several days to several weeks. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . A method of increasing the survival, stability and/or function of T cells, comprising
 providing T cells from an individual;   contacting the T cells with at least one moiety that decreases or inhibits one or more miRNAs; and   introducing the contacted T cells back into the individual.   
     
     
         14 . The method of  claim 13 , wherein the miRNA is selected from the group consisting of the miRNAs shown in Table 3. 
     
     
         15 . The method of  claim 13 , wherein the at least one moiety is selected from the group consisting of a nucleic acid molecule (e.g., RNA interference), a small molecule, a polypeptide (e.g., an antibody), and an anti-miR (e.g., an antagomir). 
     
     
         16 . The method of  claim 13 , wherein the T cells are contacted with the moiety on day 0. 
     
     
         17 . The method of  claim 13 , wherein the T cells are cultured for about 1 to about 21 days before being contacted with the moiety. 
     
     
         18 . The method of  claim 13 , wherein the T cells are contacted with the moiety for several hours to several days to several weeks. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . A method of decreasing the activity of T cells, comprising
 providing T cells from an individual;   contacting the T cells with at least one moiety that increases or induces one or more miRNAs; and   introducing the contacted T cells back into the individual.   
     
     
         22 . The method of  claim 21 , wherein the miRNA is selected from the group consisting of the miRNAs shown in Table 3. 
     
     
         23 . The method of  claim 21 , wherein the at least one moiety is selected from the group consisting of a nucleic acid molecule (e.g., RNA interference), a small molecule, a polypeptide (e.g., an antibody), and an anti-miR (e.g., an antagomir). 
     
     
         24 . The method of  claim 21 , wherein the T cells are contacted with the moiety on day 0. 
     
     
         25 . The method of  claim 21 , wherein the T cells are cultured for about 1 to about 21 days before being contacted with the moiety. 
     
     
         26 . The method of  claim 21 , wherein the T cells are contacted with the moiety for several hours to several days to several weeks. 
     
     
         27 - 34 . (canceled)