Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS

1. A method of treating an Alzheimer's Disease, the method comprising administering to an individual in need thereof a composition comprising an antibody against an Inducible T-cell COStimulator (ICOS), or an ICOS antibody fragment thereof having agonistic or activating activity,

wherein the composition is administered by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session where the composition is administered to the individual followed by a non-treatment period where the composition is not administered to the individual,

wherein the non-treatment period is longer than the treatment session, and

wherein administration of the composition transiently reduces levels of systemic immunosuppression and increases choroid plexus gateway activity in facilitating selective recruitment of immune cells into the central nervous system, thereby treating the individual.

2. The method according to claim 1 , wherein the administration of the composition during the treatment session is a single administration.

3. The method according to claim 1 , wherein the administration of the composition during the treatment session is a repeated administration.

4. The method according to claim 3 , wherein the repeated administration occurs once every two, three, four, five or six days.

5. The method according to claim 3 , wherein the repeated administration occurs once weekly.

6. The method according to claim 3 , wherein the repeated administration occurs once every four weeks.

7. The method according to claim 1 , wherein the treatment session is from 3 days to four weeks.

8. The method according to claim 7 , wherein the treatment session is from one week to four weeks.

9. The method according to claim 1 , wherein the non-treatment period is from one week to six months.

10. The method according to claim 9 , wherein the non-treatment period is from two weeks to six months.

11. The method according to claim 10 , wherein the non-treatment period is from three weeks to six months.

12. The method according to claim 1 , wherein the anti-ICOS antibody or fragment thereof is an agonistic or activating anti-ICOS antibody or fragment thereof.

13. The method according to claim 1 , wherein the anti-ICOS antibody or fragment thereof is a human or humanized anti-ICOS antibody or fragment thereof.

14. The method according to claim 1 , wherein the transient reduction in the level of systemic immunosuppression is associated with an increase in a systemic presence or activity of IFNγ-producing leukocytes and/or an increase in a systemic presence or activity of an IFNγ cytokine.

15. The method according to claim 1 , wherein the transient reduction in the level of systemic immunosuppression is associated with an increase in a systemic presence or activity of effector T cells.

16. The method according to claim 1 , wherein the transient reduction in the level of systemic immunosuppression is associated with a decrease in a systemic presence or activity of regulatory T cells and/or a decrease in a systemic presence of an IL-10 cytokine.

17. The method according to claim 1 , wherein the transient reduction in the level of systemic immunosuppression is associated with a decrease in a systemic presence of myeloid-derived suppressor cells (MDSCs).

18. The method according to claim 1 , wherein the transient reduction in the level of systemic immunosuppression occurs by release of a restraint imposed on the immune system by one or more ICOS-dependent immune checkpoints.

19. The method according to claim 18 , wherein administration of the composition blocks the one or more ICOS-dependent immune checkpoints, thereby causing the transient reduction in the level of systemic immunosuppression.

20. The method according to claim 19 , wherein the one or more ICOS-dependent immune checkpoints includes ICOS-B7RP1.

21. The method according to claim 1 , wherein the administration of the composition during the treatment session is maintained at least until a systemic presence or activity of IFNγ-producing leukocytes and/or an IFNγ cytokine rises above a reference, at which point the administration is stopped, and the non-treatment period is maintained as long as the systemic presence or activity of IFNγ-producing leukocytes and/or an IFNγ cytokine is above the reference,

wherein the reference includes

a) a level of a systemic presence or activity of IFNγ-producing leukocytes and/or an IFNγ cytokine measured in the most recent blood sample obtained from the individual before the administering; or

b) a level of a systemic presence or activity of IFNγ-producing leukocytes and/or an IFNγ cytokine characteristic of a population of individuals afflicted with the Alzheimer's Disease.

22. The method according to claim 1 , wherein a cerebral level of soluble amyloid beta peptide is reduced in the individual, a cerebral amyloid beta (Aβ) plaque burden is reduced or cleared in the individual, a hippocampal gliosis is reduced in the individual, a cerebral level of a pro-inflammatory cytokine is reduced in the individual, a brain inflammation is decreased in the individual and/or a cognitive function is improved in the individual.

23. The method according to claim 22 , wherein the improved cognitive function is learning, memory, creation of imagery, plasticity, thinking, awareness, reasoning, spatial ability, speech and language skills, language acquisition, capacity for judgment, attention or any combination thereof.

24. The method according to claim 1 , wherein the immune cells include monocytes, macrophages, or T cells.

25. The method according to claim 24 , wherein the T cells include regulatory T cells.

26. The method according to claim 24 , wherein the composition comprises the anti-ICOS antibody or fragment thereof as the only active ingredient.