MATERIALS AND METHODS FOR MODIFYING THE ACTIVITY OF T CELLS
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)