INDUCTION OF TOLERANCE IN LUNG ALLOGRAFT TRANSPLANTATION
The present disclosure relates to methods of inducing tolerance to lung allograft transplantation. These methods comprise increasing nitric oxide, increasing suppressor CD8 + T cells and/or suppressing deleterious CD8+ and CD4 + T cells.
1 . A method of inducing tolerance to a lung allograft in a subject receiving a lung allograft, the method comprising increasing the level of nitric oxide in the lung allograft in an amount sufficient to suppress the alloimmune response in the lung allograft.
2 . The method of claim 1 , wherein the level of nitric oxide is increased at the time of receipt of the lung allograft or prior to receipt of the lung allograft.
3 . The method of claim 1 , wherein the level of nitric oxide is significantly increased when compared to the level of nitric oxide in a normal lung.
4 . The method of claim 1 , wherein the level of nitric oxide is increased by increasing production of nitric oxide by graft-infiltrating recipient cells or lung allograft cells.
5 . The method of claim 1 , wherein the level of nitric oxide is increased by administering IFN-γ to the lung allograft.
6 . The method of claim 1 , wherein the level of nitric oxide is increased by administering inhaled nitric oxide to the lung allograft.
7 . The method of claim 1 , wherein the level of nitric oxide is increased by administering a nitric oxide releasing compound to the lung allograft.
8 . The method of claim 1 , wherein the level of nitric oxide is increased by inducing nitric oxide synthase activity in the allograft.
9 . The method of claim 1 , wherein the nitric oxide is increased by increasing the number of CD8 + T cells in the lung allograft.
10 . The method of claim 1 , wherein inducing tolerance to the lung allograft results in acceptance of the lung allograft for one week or longer from the time of receipt of the lung allograft.
11 . The method of claim 1 , wherein inducing tolerance to the lung allograft results in long-term acceptance of the lung allograft.
12 . A method of inducing tolerance to a lung allograft in a subject, the method comprising suppressing the alloimmune response to the lung allograft in the subject by increasing the number of CD8 + T cells in the lung allograft in an amount sufficient to suppress the alloimmune response in the lung allograft.
13 . The method of claim 12 , wherein the CD8 + T cells are CD8 + central memory T cells.
14 . The method of claim 12 , wherein the CD8 + T cells are CD8 + CCR7 + central memory T cells.
15 . The method of claim 12 , wherein the CD8+ central memory T cells are CD8+ CD44hi CD6212 hi CCR7 + central memory T cells.
16 . The method of claim 12 , wherein the CD8 + T cells are recipient CD8 + T cells.
17 . The method of claim 12 , wherein the number of CD8 + T cells is increased at the time of receipt of the lung allograft or prior to receipt of the lung allograft.
18 . The method of claim 12 , wherein the number of CD8 + T cells is significantly increased when compared to the number of CD8 + T cells in a normal lung.
19 . The method of claim 12 , wherein the number of CD8 + T cells is increased by perfusing the lung allograft with the CD8 + T cells.
20 . The method of claim 12 , wherein the alloimmune response is suppressed by suppression of CD4 + or deleterious CD8+ T cell proliferation.