Abstract: Polypeptides which comprise a receptor-ligand pair involved in T-cell activation are disclosed. Nucleic acid molecules encoding the polypeptides, and vectors and host cells for expressing the polypeptides are also disclosed. The polypeptides, or agonists and antagonists thereof, are used to treat T-cell mediated disorders.

Abstract: This invention relates to compositions and methods for cancer therapeutics. In particular, the present invention provides compositions and methods for treating tumors by inhibiting the activity of CPT1C. The methods and compositions can additionally include inhibition of glycolysis.

Abstract: Polypeptides which comprise a receptor-ligand pair involved in T-cell activation are disclosed. Nucleic acid molecules encoding the polypeptides, and vectors and host cells for expressing the polypeptides are also disclosed. The polypeptides, or agonists and antagonists thereof, are used to treat T-cell mediated disorders.

Abstract: Materials and methods are disclosed for modulating proliferation of cell types associated with Hodgkin's disease through inhibition of IL-13 and components in IL-13 associated signal transduction pathways. Methods to identify inhibitors, compositions comprising the inhibitors, and methods using the inhibitors to treat Hodgkin's disease are also disclosed.

Abstract: Materials and methods are disclosed for modulating proliferation of cell types associated with Hodgkin's disease through inhibition of IL-13 and components in IL-13 associated signal transduction pathways. Methods to identify inhibitors, compositions comprising the inhibitors, and methods using the inhibitors to treat Hodgkin's disease are also disclosed.

Abstract: Materials and methods are disclosed for modulating proliferation of cell types associated with Hodgkin's disease through inhibition of IL-13 and components in IL-13 associated signal transduction pathways. Methods to identify inhibitors, compositions comprising the inhibitors, and methods using the inhibitors to treat Hodgkin's disease are also disclosed.

Abstract: Materials and methods are disclosed for modulating proliferation of cell types associated with Hodgkin's disease through inhibition of IL-13 and components in IL-13 associated signal transduction pathways. Methods to identify inhibitors, compositions comprising the inhibitors, and methods using the inhibitors to treat Hodgkin's disease are also disclosed.

Abstract: Non-human mammals comprising a disrupted MSH2 gene are disclosed. More particularly, animals having a disruption in one or both alleles of the MSH2 gene or a homolog of the MSH2 gene are disclosed. Animals homozygous for the disruption are viable past the embryonic stage of development but show an increased incidence of lymphoma, intestinal adenomas and carcinomas, and squamous cell tumors of the skin. Specifically disclosed are mice whose genome comprises a disrupted MSH2 gene such that the mice exhibits an increase in the incidence of spontaneous lymphoma over the incidence of spontaneous lymphoma in wild type mice.

Abstract: Interferon regulatory factor-1 (IRF-1) is implicated in the regulation of type I interferons (IFN) and cell growth. The invention is a mutant mouse lacking expression of the IRF-1 gene. Mice lacking IRF-1 did not differ from normal mice in size, behaviour, or reproductive ability. With fibroblasts derived from these mutant mice, it was shown that type I IFN induction is dramatically reduced when cells are induced by poly(I):poly(C). In contrast, no differences were found when cells are induced by New Castle Disease Virus (NDV), or induced by poly(I):poly(C) with prior treatment of IFN-.beta.. On the other hand, the induction levels of IFN-inducible genes such as MHC class I and 2'-5' oligoadenylate synthetase (2'5'OAS) were not affected. Collectively, these results illustrate an IRF-1 independent mechanism of gene induction for type I IFN and these IFN-inducible genes. The critical role of IRF-1 in the immune system has been documented for the first time by the observation that the number of TcR.alpha..beta..

Abstract: A mutant mouse strain without CD4 expression has been generated by disrupting the CD4 gene using embryonic stem cell technology. In these mice CD4.sup.+ T lymphocytes are not present in peripheral lymphoid organs, but the development of CD8.sup.+ T cells and myeloid components is unaltered, indicating that expression of CD4.sup.+ on progenitor cells and CD4.sup.+ CD8.sup.+ (double positive) thymocytes is not obligatory. These mice have markedly decreased helper cell activity for antibody responses, whereas cytotoxic T cell activity against viruses was within normal range of that generated by CD4.sup.+ mice. This differential requirement for CD4.sup.+ helper T cells has important implications for the understanding of the immune function in a variety of immune disorders, including AIDS, in which the CD4.sup.+ cells are reduced or absent.

Abstract: The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 and 75 kDa. Mutant mice of the invention lacking tumor necrosis factor receptor (TNFR) p55 still express functional TNFRp75 molecules at the cell surface. Normal weight and size of the mutant mice are not altered. Thymocyte development and lymphocyte populations are normal, and clonal deletion of potentially self-reactive T cells is not impaired. Activation of the nuclear transcription factor .kappa.B (NF-.kappa.B), however, is completely abrogated after stimulation with TNF. Moreover, TNFRp55 mutant mice are protected from septic shock induced by bacterial endotoxin or superantigen, but Listeria clearance is severely impaired and mutant mice easily succumb to Listeria infection. Thus, the two TNF receptors are not redundant, are independently controlled, and play different roles in normal and pathological physiology.

Abstract: The transcription factors, IRF-1 and IRF-2 are induced by interferons (IFNs) and a variety of other cytokines. IRF-1 functions as an activator whereas IRF-2 represses IRF-1 action by competing for binding to the same cis-elements. Recently, it has been shown that balanced expression between these two factors is critical for maintaining normal restraints on cell growth. Mutant mice deficient for IRF-2 were prepared by homologous recombination. In mutant cells, infection by Newcastle disease virus (NDV) resulted in the induction of type I IFN (IFN-.alpha. and IFN-.beta.) mRNAs, the levels of which were significantly higher than in wild type cells; whereas, such a difference was not found upon induction by poly(I):poly(C). Unlike the IRF-1 deficient mutant mice, the IRF-2 deficient mice of the invention exhibit multiple phenotypes of physical vulnerability, including lethality to lymphocytic choriomeningitis virus (LCMV).

Abstract: A mutant non-human mammal lacking expression of the lymphocyte-specific tyrosine kinase p56.sup.lck. Lck deficient mice possess few peripheral T lymphocytes and a pronounced thymic atrophy. The remaining thymus contains immature thymocytes surrounded by a perturbed thymic microenvironment. p56.sup.lck appears to play a crucial role in early thymocyte differentiation.

Abstract: Mice lacking expression of CD28 or particular CD45 isoforms in certain cells of the immune system are provided. Also provided are methods of using these mice.

Abstract: Mice lacking expression of CD28 or particular CD45 isoforms in certain cells of the immune system are provided. Also provided are methods of using these mice.

Abstract: A mouse lacking expression of a subunit of the IL-2 receptor in certain cells of the immune system is provided. Also provided are methods of using such mice.

Abstract: A mutant mouse strain without CD8 (Lyt-2 and Lyt-3) expression on the cell surface has been generated by disrupting the Lyt-2 gene using embryonic stem cell technology. In these mammals, for example, mice, CD8.sup.+ T lymphocytes are not present in peripherial lymphoid organs, but the CD4.sup.+ T lymphocyte population seems to be unaltered. Cytotoxic response of T lymphocytes from these mice against alloantigens and viral antigens is dramatically decreased. Proliferative response against alloantigens and in vivo help to B lymphocytes, however, are not effected. These mice should be useful for drug development and for studies of diseases of the immune system such as, autoimmunity, immunodeficiency, transplant rejection and tumor rejection.

Abstract: The invention provides a nucleic acid having a sequence which encodes a polypeptide that is at least part of a T cell antigen receptor. This encoded sequence is about 936 nucleotides in length and preferably is a human T cell antigen receptor. The nucleic acid sequence of one embodiment of the invention is shown in FIG. 3.The nucleic acid sequence may be used as a probe to determine whether an unknown cell, e.g., a tumor cell, is a T cell.Polypeptides encoded by the nucleic acid sequence include about 312 amino acids and are at least part of a T cell antigen receptor. They include at least one sequence which over 21 contiguous amino acids has greater than about 35% homology with mouse and human immunoglobin .lambda. light chains.Antibody to the polypeptide may be prepared and used to identify T cell antigen receptor and to determine whether an unknown cell, e.g., a tumor cell, is a T cell.

Abstract: The invention provides a nucleic acid having a sequence which encodes a polypeptide that is at least part of a T cell antigen receptor. This encoded sequence is about 936 nucleotides in length and preferably is a human T cell antigen receptor. The nucleic acid sequence of one embodiment of the invention is shown in FIG. 3.The nucleic acid sequence may be used as a probe to determine whether an unknown cell, e.g., a tumor cell, is a T cell.Polypeptides encoded by the nucleic acid sequence include about 312 amino acids and are at least part of a T cell antigen receptor. They include at least one sequence which over 21 contiguous amino acids has greater than about 35% homology with mouse and human immunoglobin .lambda. light chains.Antibody to the polypeptide may be prepared and used to identify T cell antigen receptor and to determine whether an unknown cell, e.g., a tumor cell, is a T cell.

Abstract: The invention provides a composition for application to a metal surface, the composition comprising an inorganic nitrite, a benzoate and a carbonate in aqueous solution. The composition may advantageously be used as a lubricant or coolant during metal working, for example temper rolling, and for protection of coil or sheet packs of steel against corrosion.