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

Human T lymphocyte proliferative response induced via CD28 molecule is analyzed. An anti CD28 MoAb, CLB-CD28/1, induces the proliferation of human peripheral blood mononuclear cells in the absence of other stimuli, indicating that CD28 molecule can directly mediate a mitogenic signal in this system. The mitogenic activity of MoAb CLB-CD28/1 on PBMC does not require MoAb interaction with monocyte Fc receptors, since F(ab')2 fragments from the MoAb are mitogenic to the same extent as whole IgG. Nevertheless, the activity depends on the presence of accessory cells, since purified T lymphocytes require addition of irradiated monocytes and interleukin 2 to proliferate when incubated with MoAb CLB-CD28/1. On the other hand, MoAb CLB-CD28/1 induces response to IL-2 in thymocytes in the absence of accessory cells. Cooperation of MoAb CLB-CD28/1 with three other MoAbs, recognizing CD3, CD5 and HLA Class I antigens, respectively, induces Tac antigen expression and IL-2 responsiveness in purified T lymphocytes. This effect is obtained without cross-linking of the MoAb. It does not rely on a physical association between CD28 and CD3, CD5 or HLA Class I molecules, as demonstrated by co-modulation experiments. These data indicate that expression of IL-2 receptor on T lymphocytes can result from interaction of multiple activation pathways and that some of them, such as those mediated by CD5 and HLA Class I antigens, previously reported to serve as modulatory circuits, can instead act as essential elements in the onset of T lymphocyte proliferation.
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PMID:Mitogenic activity of anti-CD28 MoAb CLB-CD28/1 on peripheral blood mononuclear cells and its cooperation with other anti-T cells MoAb in the activation of purified T lymphocytes. 170 Oct 62

The NF-kappa B/rel family of transcription factors regulates the expression of a number of genes, including interleukin 2 (IL-2), IL-2 receptor alpha chain (Tac), and others, controlling T lymphocyte activation. The CD28 antigen is involved in regulation of T cell activation. To investigate whether CD28 antigen regulates NF-kappa B factors, we analyzed the effect of an anti-CD28 monoclonal antibody (mAb), CLB-CD28/1, on the nuclear activity of NF-kappa B complexes in resting and CD3-activated peripheral blood mononuclear cells (PBMC) of 11 donors. Cells were incubated with or without the anti-CD3 mAb OKT3 and/or the mAb CLB- CD28/1. Then nuclear extracts were obtained and analyzed for their binding to a 32P-labeled oligonucleotide, corresponding to the NF-kappa B 5'-CAACGGCAGGGGAATCTCCCTCTCCTT-3' consensus sequence in electrophoretic mobility shift assays. PBMC incubated with control medium did not appear to contain significant levels of NF-kappa B nuclear activity. The anti-CD28 mAb did not induce any detectable NF-kappa B nuclear activity in PBMC when used alone, except for two cases. However, cells incubated with the anti-CD3 mAb displayed NF-kappa B nuclear activity in 7 of the 11 cases. The addition of anti-CD28 to the anti-CD3 mAb-stimulated cells enhanced the levels of NF-kappa B activity in eight PBMC, while it did not modify PBMC in one sample and partially inhibited the induction of NF-kappa B in the remaining two samples. The stimulatory effect of anti-CD28 mAb on NF-kappa B nuclear activity was detected also on CD3-stimulated purified T lymphocytes. By analysis with antisera recognizing the p50 and p65 components of the NF-kappa B/rel family, NF-kappa B complexes of CD3+CD28-stimulated PBMC were found to contain both p50 and p65 proteins. An enhanced production of IL-2 was detected in cultures of CD3+CD28-stimulated PBMC. Our results indicate that CD28 triggering can modulate the activity on NF-kappa B nuclear complexes in T lymphocytes stimulated via CD3. Such an effect appeared not to require the presence of accessory cells (AC) or AC-derived cytokines.
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PMID:Regulation of NF-kappa B nuclear activity in peripheral blood mononuclear cells: role of CD28 antigen. 802 54