Abstract: Methods and compositions for the identification of novel targets for diagnosis, prognosis, therapeutic intervention and prevention of an immune disorder. In particular, the present invention is directed to the identification of novel targets which are anergy markers. The present invention is further directed to methods of high-throughput screening for test compounds capable of modulating the activity of proteins encoded by the novel targets. Moreover, the present invention is also directed to methods that can be used to assess the efficacy of test compounds and therapies for the ability to inhibit an immune disorder. Methods for determining the long term prognosis in a subject are also provided.

Abstract: Isolated peptide fragments of the conserved regulatory domain of NFAT protein capable of inhibiting protein-protein interaction between calcineurin and NFAT, or a biologically active analog thereof are described. Isolated polynucleotides and gene therapy vectors encoding such peptide fragments are also described. In addition, methods for treating immune-related diseases or conditions and methods for high throughput screening of candidate agents are described. Pharmaceutical compositions are also provided.

Abstract: The invention concerns the use of functional derivatives of ICAM-1 to treat viral infection. The invention also provides a vaccine to prevent such infection, and a diagnostic assay to determine the existence and extent of such infection.

Abstract: A method for the enrichment of dendritic cells from the peripheral blood of a mammal is described. Peripheral blood having mononuclear cells from a mammal is provided. The mononuclear cells are separated from the peripheral blood. The mononuclear cells are separated into a first cell population having substantially lymphocytes and a second cell population having substantially myeloid cells. The myeloid cells are separated into a third cell population having substantially monocytes and a fourth cell population having substantially dendritic cells. Also described are purified dendritic cell populations, vaccine compositions and methods for the treatment of cancer using dendritic cells, and kits useful for the enrichment of dendritic cells from blood.

Abstract: The present invention relates to the discovery of novel genes encoding Monocyte Chemotactic Protein-5 (MCP-5) polypeptides. Therapeutics, diagnostics and screening assays based on these molecules are also disclosed.

Abstract: A method for determining the immunocompetence of a mammal is described. Bodily fluid having T cell receptor complexes from a mammal is provided. Expression of a first component and a second component of the T cell receptor complexes is evaluated. An abnormal ratio of the number of cells expressing the first component as compared to the number of cells expressing the second component indicates altered immunocompetence in the mammal.

Abstract: A method for the enrichment of dendritic cells from the peripheral blood of a mammal is described. Peripheral blood having mononuclear cells from a mammal is provided. The mononuclear cells are separated from the peripheral blood. The mononuclear cells are separated into a first cell population having substantially lymphocytes and a second cell population having substantially myeloid cells. The myeloid cells are separated into a third cell population having substantially monocytes and a fourth cell population having substantially dendritic cells. Also described are purified dendritic cell populations, vaccine compositions and methods for the treatment of cancer using dendritic cells, and kits useful for the enrichment of dendritic cells from blood.

Abstract: It has been found that agents which inhibit the interaction between the band 3 protein and its ligand (hereafter sometimes referred to as “interaction inhibitors” or “inhibitors”), CD36/thrombospondin, can also be used to enhance thrombolysis. The inhibitors can be peptides which contain sequences present in exofacial loops of the band 3 protein, or can be non-natural, D-isomer forms of the same sequences, or can be peptides, peptidomimetics, or non-peptidic molecules which interfere with band 3 protein—ligand interactions. One preferred group of such inhibitors comprises peptides characterized by the sequence motif Z2Z3Z2UX−UUUX− (SEQ ID NO:44), wherein Z2 represents a hydrophobic residue, U represents unobstructive residues, Z3 is either Z2 or an unobstructive residue and X− represents negatively charged residues.

Abstract: The present invention relates to intercellular adhesion molecules (ICAM-3) which is involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes therapeutic and diagnostic uses for adhesion molecules and for the antibodies that are capable of binding them.

Abstract: The present invention is based on the novel observation that upon stimulation of resting myeloid cells, not all of the Mac-1 molecules expressed by the cell become activated. Only select subpopulations of Mac-1 molecules are activated and become capable of binding ligand. Further, the activated Mac-1 molecules were found to possess activation specific epitopes which distinguishes them from non-activated Mac-1 molecules. Based on these observations antibodies are described which selectively bind activated Mac-1 molecules but are substantially incapable of binding non-activated Mac-1.

Abstract: A new human elastase inhibitor is provided. The human monocyte elastase inhibitor is isolated, purified, characterized at the molecular level and cloned. The human monocyte elastase inhibitor is capable of forming a covalent complex with elastase or Proteinase-3 and is capable of inhibiting elastase.

Abstract: A method for finding an agent which inhibits interaction between LIL-Stat protein and a nucleic acid having a LIL-Stat binding sequence is described. The LIL-Stat protein is contacted with the nucleic acid in the presence of an agent which inhibits or does not inhibit the interaction between the LIL-Stat protein and the nucleic acid. It is determined whether or not the agent inhibits this interaction. Also described are a method for treating an inflammatory response in a mammal, a therapeutic inhibitory agent suitable for treating or preventing an inflammatory response in a mammal, and DNA molecules having a DNA sequence encoding a binding site for the LIL-Stat protein.

Abstract: A new human elastase inhibitor is provided. The human monocyte elastase inhibitor is isolated, purified, characterized at the molecular level and cloned. The human monocyte elastase inhibitor is capable of forming a covalent complex with elastase or Proteinase-3 and is capable of inhibiting elastase.

Abstract: The present invention relates to intercellular adhesion molecules (ICAM-3) which is involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes therapeutic and diagnostic uses for adhesion molecules and for the antibodies that are capable of binding them.

Abstract: The present invention is directed to a method for isolating a novel receptor for .alpha.4 integrins such as VLA-4, that is distinct from VCAM-1 and from fibronectin. Isolated nucleic acids encoding the receptor and antibodies to the receptor are also provided. The invention is also directed to pharmaceutical compositions, and methods of treating disorders involving an undesirable inflammatory or immune response by administering the VLA-4 receptor of the invention.

Abstract: The present invention relates to a novel assay for lymphocyte chemotaxis. The assay is transendothelial assay using endothelial cells cultured on microporous filters. Lymphocyte transmigration through the filter toward a suspected chemoattractant is measured. Apparatuses for carrying out the assay are also provided. The apparatuses and methods of the present invention can be used for the identification of inhibitors (e.g., antagonists) or promoters (chemoattractants) of the adhesion receptor-mediated migration of leukocytes through the endothelium (extravasation). Such inhibitors and promoters respectively inhibit and promote the inflammatory response, and thus have therapeutic utilities. The inhibitors and promoters are identified by detecting their abilities to respectively inhibit or promote the chemotaxis of lymphocytes in the assay of the invention. The assay of the invention also has diagnostic utilities for detecting a disease or disorder involving a defect in lymphocyte chemotaxis.

Abstract: The present invention provides in vitro models of the in vivo rolling and arrest of leukocytes along the endothelial cell wall, which are important steps in the migration of leukocytes out of the blood stream and into tissue, as part of the inflammatory response. The in vitro models of the invention are functional under physiologic flow conditions resulting in physiologic shear stresses. In a specific embodiment, for modelling leukocyte rolling, the apparatus of the invention comprises a solid phase surface with rolling mediator molecules present thereon. Such rolling mediators are, for example, selectins and selectin ligands which have binding partners expressed on leukocytes. In another specific embodiment, for modelling leukocyte rolling followed by adhesion/arrest, the apparatus of the invention comprises a solid phase surface with both rolling mediators and integrin binding partners present thereon.

Abstract: A cloned gene encoding a new human elastase inhibitor is provided. The cloned gene is isolated, purified, and sequenced. The cloned gene encoding a human elastase inhibitor that is substantially non-glycosylated, is capable of forming a covalent complex with elastase and is capable of inhibiting elastase.

Abstract: Method for storing, preserving and transporting concentrates of human platelets under blood bank conditions prior to transfusion by compressing plastic walled platelet bags with the use of a grid to permit gas circulation to the bag with the bag positioned for storage in a desired position. A grid aids in storing and preserving platelets and has a rigid body with a substantial open area configured to substantially compress a side of a plastic walled platelet bag to form a substantially uniform layer of fluid in the bag to maximize gas transfer capacity and permit long storage life at atmospheric conditions without the need for conventional agitation of the bag.