Abstract: The present invention provides binding molecules that specifically bind to GITR, e.g., human GITR (hGITR), on T cells and dendritic cells. Binding molecules of the invention are characterized by binding to hGITR with high affinity, in the presence of a stimulating agent, e.g., CD3, are agonistic, and abrogate the suppression of Teff cells by Treg cells. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such binding molecules. Methods of using a binding molecule of the invention to detect human GITR or to modulate human GITR activity, either in vitro or in vivo, are also encompassed by the invention.

Abstract: Inducing tolerance in a primate by use of a compound, or a combination of at least two compounds, that has certain characteristics when tested in vitro. The compound, alone or in combination, is preferably TRX1 antibody and the compound or combination is preferably used in accordance with a specified dosing regimen.

Abstract: The present invention provides binding molecules that specifically bind to ILT3, e.g., human ILT3 (hILT3), on antigen presenting cells, such as for example, monocytes, macrophages and dendritic cells (DC), e.g., monocyte-derived dendritic cells (MDDC). The binding molecules of the invention are characterized by binding to hILT3 with high affinity and downmodulating immune responses in vitro, e.g., downmodulating alloimmune responses; the production of inflammatory cytokines by dendritic cells, e.g., monocyte-derived dendritic cells (MDDC); the upregulation of costimulatory molecules by DC, e.g., MDDC; and/or calcium flux in monocytes. In addition, the binding molecules upregulate the expression of inhibitory receptors on dendritic cells, e.g., immature dendritic cells. Surprisingly, these same binding molecules which downmodulate immune responses in vitro, are immunostimulatory in vivo. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof.

Abstract: The present invention provides binding molecules that specifically bind to GITR, e.g., human GITR (hGITR), on T cells and dendritic cells. Binding molecules of the invention are characterized by binding to hGITR with high affinity, in the presence of a stimulating agent, e.g., CD3, are agonistic, and abrogate the suppression of Teff cells by Treg cells. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such binding molecules. Methods of using a binding molecule of the invention to detect human GITR or to modulate human GITR activity, either in vitro or in vivo, are also encompassed by the invention.

Abstract: The present invention provides binding molecules that specifically bind to ILT3, e.g., human ILT3 (hILT3), on antigen presenting cells, such as for example, monocytes, macrophages and dendritic cells (DC), e.g., monocyte-derived dendritic cells (MDDC). The binding molecules of the invention are characterized by binding to hILT3 with high affinity and downmodulating immune responses in vitro, e.g., downmodulating alloimmune responses; the production of inflammatory cytokines by dendritic cells, e.g., monocyte-derived dendritic cells (MDDC); the upregulation of costimulatory molecules by DC, e.g., MDDC; and/or calcium flux in monocytes. In addition, the binding molecules upregulate the expression of inhibitory receptors on dendritic cells, e.g., immature dendritic cells. Surprisingly, these same binding molecules which downmodulate immune responses in vitro, are immunostimulatory in vivo. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof.

Abstract: The present invention is based, at least in part, on the finding that tolerance can be induced by inhibition of CD4+ cells (and optionally CD8+ cells). Accordingly, the optimized dosing methods of the invention are useful in treating a primate, e.g., a human, by inhibiting CD4+ T cells to induce tolerance to at least one antigen, e.g., self or foreign, such as for inducting tolerance in a primate against a soluble or a cell bound antigen (e.g., an allogeneic or xenogeneic transplanted antigen).

Abstract: The invention provides methods (also referred to herein as a “screening assays”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) capable of modulating tolerance. In one embodiment, the invention provides methods for identifying a tolerance modulatory compound, comprising, e.g., contacting a T cell with a stimulating agent and a test compound and assaying for expression or activity of at least one T regulatory (Treg) marker and at least one T effector (Teff) marker.

Abstract: The present invention is based, at least in part, on the finding that tolerance can be induced by inhibition of CD4+ and CD8+ T cells. Accordingly, the methods of the invention are useful in treating a primate, e.g., a human, by inhibiting CD4+ and CD8+ T cells to induce tolerance to at least one antigen, e.g., self or foreign, such as for inducting tolerance in a primate against a transplanted antigen, e.g., an allogeneic or xenogeneic transplanted antigen.

Abstract: The present invention is based, at least in part, on the discovery of certain genes which are absent from T regulatory cells and present on effector T cells (Th1 and Th2), e.g., Protein Kinase C Theta (PKC theta). Furthermore, a pathway essential for the production of inflammatory cytokines and cellular proliferation of inflammatory, effector T cells is not utilized by regulatory T cells. Accordingly, in one aspect the invention provides. methods for promoting regulatory T cell function in immune cells relative to effector T cell function, comprising contacting immune cells with an agent that inhibits a protein kinase C theta pathway in the immune cells. In another aspect, the invention provides methods for treating a subject having a condition that would benefit from promoting regulatory T cell function relative to effector T cell function in the subject, comprising administering an agent that inhibits a protein kinase C theta pathway in immune cells of the subject.