Abstract: The invention relates to methods of modulating immune responses in a subject such as by administering to the subject agents which modulate tim-1, tim-2 or tim-4 activity, or which modulate the physical interaction between tim-1 and tim-4 or between tim-2 and a tim-2 ligand. Immune responses include, but are not limited to, autoimmune disorders, transplantation tolerance, and Th1 and Th2-mediated responses and disorders. The invention also relates to novel assays for identifying agents which modulate the physical interaction between tim-1 and tim-4. In addition, the invention relates to novel soluble tim-4 polypeptides and to nucleic acids which encode them.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: The present invention features compositions for inhibiting both the IL-6 and the IL-21 pathways and methods of making and using such compositions. Our work to date indicates the importance of the redundancy of IL-6 and IL-21 to perform certain crucial functions. The pathways can be inhibited by inhibiting the ligands (i.e., IL-6 and IL-21) and/or their respective receptors (i.e., the IL-6 receptor and IL-21 receptor). Alternatively, or in addition, upstream and downstream effectors in the IL-6 and IL-21 pathways can be blocked. The agents used can be antibody or antibody-based proteins or peptides including circulating receptors, optionally coupled to an immunoglobulin or a portion thereof (e.g., the Fc region). Also provided are methods for using the compositions, for example, in organ transplantation, tissue grafting, or autoimmune disorders.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: The invention relates to methods of modulating immune responses in a subject, such as by administering to the subject agents which modulate tim-1, tim-2 or tim-4 activity, or which modulate the physical interaction between tim-1 and tim-4 or between tim-2 and a tim-2 ligand. Immune responses include, but are not limited to, autoimmune disorders, transplantation tolerance, and Th1 and Th2-mediated responses and disorders. The invention also relates to novel assays for identifying agents which modulate the physical interaction between tim-1 and tim-4. In addition, the invention relates to novel soluble tim-4 polypeptides and to nucleic acids which encode them.

Abstract: The invention relates to methods of modulating immune responses in a subject, such as by administering to the subject agents which modulate tim-1, tim-2 or tim-4 activity, or which modulate the physical interaction between tim-1 and tim-4 or between tim-2 and a tim-2 ligand. Immune responses include, but are not limited to, autoimmune disorders, transplantation tolerance, and Th1 and Th2-mediated responses and disorders. The invention also relates to novel assays for identifying agents which modulate the physical interaction between tim-1 and tim-4. In addition, the invention relates to novel soluble tim-4 polypeptides and to nucleic acids which encode them.

Abstract: The invention relates to methods of inducing tolerance and preventing transplant rejection by blocking costimulatory signals and using immunosuppressive agents, preferably rapamycin, to prevent late rejection episodes, yet not block tolerance inducing T-cell specific depletion; compositions and kits for use in such methods are also provided herein.

Abstract: Disclosed herein are mutant IL-15 polypeptides and methods for using these polypeptides to modulate the immune response in a patient.

Abstract: Disclosed are methods for inhibit rejection of a graft in a patient. The methods involve treating the graft with a molecule which binds to a co-stimulatory protein of antigen-presenting cells. Useful molecules include chimeras having enzymatically inactive polypeptides bonded to polypeptides which bind to co-stimulatory proteins of antigen-presenting cells. Also disclosed, are chimeric molecules composed of lytic IgG Fc bonded to CD2, CD28, CD40L, or CTLA-4. In addition, disclosed are methods for inhibiting rejection of a graft in a patient; the methods involve treating the brain-dead, beating heart donor of the graft, prior to removal of the graft from the donor, to render the graft less susceptible to rejection by the patient.

Abstract: The present invention features prognostic methods useful in assessing patients who have received a transplant and reagents, optionally packaged as kits or organized as arrays, that can be used to carry out those methods. The inventions are based, in part, on our analysis of gene expression in renal allografts and clinical parameters, such as the age of the donor. The clinical parameters include one or more variables associated with the recipient (e.g., the recipient's age and/or race); one or more variables associated with the graft (e.g., whether the graft is obtained from a living donor or a cadaver and the ischemic time); and variables associated with the donor (e.g., the donor's age and/or race). The genes that can be assessed include those encoding agents that mediate inflammation, immune activation, and cell death (we may refer to these genes below as “inflammatory”, “immune” or “cytoprotective”).

Abstract: The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.

Abstract: Disclosed are chimeric proteins having a cytokine fused to an enzymatically inactive polypeptide which increases the circulating half-life of the cytokine. The chimeric proteins are useful for treating, inhibiting, or preventing a variety of conditions, including septic shock, granulomatous disorders, Type I diabetes, and various cancers (e.g., multiple myeloma) in a patient.

Abstract: Mutant IL-15 polypeptides and compositions including the polypeptides are described herein. In various embodiments, a mutant IL-15 polypeptide is joined to a heterologous polypeptide. Also described herein are uses of the mutant IL-15 polypeptides, e.g., in suppressing immune responses.

Abstract: The invention features methods of treating patients who have received, or who are scheduled to receive, a heart, lung, or heart-lung transplant by administering to the patient an agent that antagonizes IL-15 or the IL-15 receptor (IL-15R).

Abstract: The invention relates to methods of modulating immune responses in a subject, such as by administering to the subject agents which modulate tim-1, tim-2 or tim-4 activity, or which modulate the physical interaction between tim-1 and tim-4 or between tim-2 and a tim-2 ligand. Immune responses include, but are not limited to, autoimmune disorders, transplantation tolerance, and Th1 and Th2-mediated responses and disorders. The invention also relates to novel assays for identifying agents which modulate the physical interaction between tim-1 and tim-4. In addition, the invention relates to novel soluble tim-4 polypeptides and to nucleic acids which encode them.

Abstract: Disclosure herein are mutant IL-15 polypeptides and methods for using these polypeptides to modulate the immune response in a patient.

Abstract: The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

Abstract: Disclosed are chimeric proteins having IL-10 fused to an enzymatically inactive polypeptide which increases the circulating half-life of IL-10. The chimeric polypeptides are useful for treating or preventing septic shock, inhibiting the development of Type I diabetes, and treating multiple myeloma in a patient.

Abstract: The invention relates to methods of inducing tolerance and preventing transplant rejection by blocking costimulatory signals and using immunosuppressive agents, preferably rapamycin, to prevent late rejection episodes, yet not block tolerance inducing T-cell specific depletion; compositions and kits for use in such methods are also provided herein.

Abstract: The invention relates to compounds, such as proteins, peptides and organic compounds, capable of blocking or inhibiting the binding interaction of Raf-1 or 14-3-3 proteins to the &bgr; chain of IL-2, and pharmaceutical compositions containing such compounds. In vitro assays for isolating, identifying and characterizing such compound capable of inhibiting interaction of Raf-1 or 14-3-3 proteins to IL-2&bgr; are also provided.