Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In transgenic mice expressing a mutated T cell receptor (TCR) beta chain lacking the variable domain (DeltaV-TCRbeta) T cell differentiation is arrested at the CD4+ CD8+ thymocyte stage. Here, we report that these transgenic animals develop CD4+, CD8+, IL-2 receptor alpha-positive T cell lymphomas at a very high incidence. Introduction of a normal TCRbeta gene into the DeltaV-TCRbeta transgenic mice drastically reduces the tumor incidence, while crossing the DeltaV-TCRbeta transgene onto a recombinase-deficient RAG-1-/- background does not prevent tumor development. Therefore, the induction of T cell lymphomas is a property of the mutated TCRbeta chain. The DeltaV-TCRbeta chain appears at the cell surface as a disulfide-linked DeltaV-TCRbeta/pTalpha dimer in association with CD3gamma and -episilon, but not with CD3delta. This mutated preTCR/CD3 complex is shown to induce pre-T cell proliferation and differentiation, but does not permit formation of a normally sized CD4+8+ thymic compartment. DeltaV-TCRbeta transgenic mice frequently show an expansion of CD4+8+, IL-2 receptor alpha+ pre-T cells early in life. These cells likely represent the population that is subject to oncogenic transformation.
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PMID:Oncogenic potential of a pre-T cell receptor lacking the TCR beta variable domain. 866 34

Programmed cell death, or apoptosis, is important in homeostasis of the immune system: for example, non-functional or autoreactive lymphocytes are eliminated through apoptosis. One member of the tumour necrosis factor receptor (TNFR) family, Fas (also known as CD95 or Apo-1), can trigger cell death and is essential for lymphocyte homeostasis. FADD/Mort1 is a Fas-associated protein that is thought to mediate apoptosis by recruiting the protease caspase-8. A dominant-negative mutant of FADD inhibits apoptosis initiated by Fas and other TNFR family members. Other proteins, notably Daxx, also bind Fas and presumably mediate a FADD-independent apoptotic pathway. Here we investigate the role of FADD in vivo by generating FADD-deficient mice. As homozygous mice die in utero, we generated FADD-/- embryonic stem cells and FADD-/- chimaeras in a background devoid of the recombination activating gene RAG-1, which activates rearrangement of the immunoglobulin and T-cell receptor genes. We found that thymocyte subpopulations were apparently normal in newborn chimaeras. Fas-induced apoptosis was completely blocked, indicating that there are no redundant Fas apoptotic pathways. As these mice age, their thymocytes decrease to an undetectable level, although peripheral T cells are present in all older FADD-/- chimaeras. Unexpectedly, activation-induced proliferation is impaired in these FADD-/- T cells, despite production of the cytokine interleukin (IL)-2. These results and the similarities between FADD-/- mice and mice lacking the beta-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis.
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PMID:Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. 952 26

Omenn syndrome (OS) was reported until recently as a distinct form (phenotype and genotype) of severe combined immunodeficiency (SCID). Similar to other patients with SCID, patients with OS present early in infancy with viral or fungal pneumonitis, chronic diarrhea, and failure to thrive. Unlike typical SCID, patients with OS have enlarged lymphoid tissue, severe erythroderma, increased IgE levels, and eosinophilia. The inflammation observed in these patients is believed to be triggered by clonally expanded T cells, which are predominantly of the T(H)2 type. These abnormal T cells, in the absence of proper regulation by other components of the immune system, secrete a host of cytokines that promote autoimmune as well as allergic inflammation. The emergence of these T-cell clones occurs in patients with hypomorphic mutations in recombination activating gene 1 or 2, but not in patients with deleterious mutations in these enzymes which render them inactive. Recently, OS was also identified in a growing list of other leaky SCIDs with mutations in RNA component of mitochondrial RNA processing endoribonuclease, adenosine deaminase, IL-2 receptor gamma, IL-7 receptor alpha, ARTEMIS, and DNA ligase 4. This new information revealed OS is a distinct inflammatory process that can be associated with genetically diverse leaky SCIDS.
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PMID:Omenn syndrome: inflammation in leaky severe combined immunodeficiency. 1899 30