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)

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
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PMID:Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein. 135 46

Uncertainty has existed as to whether a T-cell deficiency exists in human immunodeficiency virus (HIV) infection different from that inherent in the reduced T-cell numbers characteristic of the disease. Heretofore, methods for measuring T-cell responses in patients have been carried out with systems requiring monocytes as accessory cells. In the presence of high concentrations of interleukin-2, however, highly purified T cells respond in a monocyte-independent fashion to antibody reactive with the CD3 component of the antigen receptor complex Ti/CD3. Highly purified T cells of HIV-infected patients responded subnormally in this anti-CD3/IL-2 system, even in the case of patients who were asymptomatic or had only lymphadenopathy. The defective T-cell responses occurred over a wide range of concentrations of the anti-CD3. Neither poor IL-2 receptor function as reflected by responses to limiting dilutions of IL-2 nor IL-1 receptor function as defined by incremental proliferation when IL-1 is added accounted for this defect, which also correlated poorly with T4 and T8 numbers. These results suggested that the T-cell abnormality was closely related to Ti/CD3 function, was not specifically or restrictively associated with T4 cells, and was not due to defective IL-2- or IL-1-receptor functions. The amount of HIV RNA in 10(5) T lymphocytes from the patients amounted to less than that found in one cell of a standard HIV infected laboratory cell line (CEM), using slot-blot hybridization. Thus the T-cell deficiency we have observed was not likely to be due directly to cell killing by HIV resident in the T4 cells. Other factors may be important in inducing the immunodeficiency, some of which are discussed.
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PMID:Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus. 278 31

A recombinant amphotropic retrovirus was used to introduce the protein-coding region of the IL-2 receptor cDNA derived from HUT-102 cells into human CEM leukemic T-cells that lack these receptors. CEM T-cells that contained the virus expressed functional IL-2 receptors that transiently mediated five- to tenfold increases in [3H]thymidine incorporation following the addition of picomolar quantities of IL-2. Although IL-2 responsiveness was subsequently lost, it could be reinduced by cellular activation with the OKT11 monoclonal antibody. This phenotype also proved unstable with progressive time in culture. Despite the loss of IL-2 responsiveness, the infected CEM T-cells continued to express Tac antigen and displayed 50 to 200 high-affinity IL-2 receptors per cell that bound IL-2 with a dissociation constant of 4.3 pM. This affinity is fully equivalent to that detected on activated normal T-cells (2 to 50 pM). The apparent molecular size of the Tac antigen on these cells (55,000 to 60,000 daltons) was comparable to that on normal activated T-cells but 5000 daltons larger than the aberrant IL-2 receptors on HUT-102 cells. These data demonstrate that expression of a human IL-2 receptor cDNA in human T-cells results in high-affinity IL-2 receptor display that transiently imparts an IL-2 responsive state of growth. These results also raise the possibility that the T11 surface receptor may play an important regulatory role in high-affinity IL-2 receptor expression.
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PMID:Reconstitution of high affinity IL-2 receptor expression in a human T-cell line using a retroviral cDNA expression vector. 311 93

The use of baboons as a model for the study of allo- and xenotransplantation has become increasingly important, but there are few studies on the basic immunological responses in baboons that might be relevant for a rejection reaction. In present study, the cell-surface phenotype, cytokine-induced activation and growth, and cytotoxicity of baboon and human natural killer (NK) and lymphokine-activated killer (LAK) cells were compared. A panel of murine monoclonal antibodies specific for human cell-surface markers expressed on lymphocytes was used to compare relevant baboon and human peripheral blood lymphocytes (PBL). Baboon PBL were 52.1+/-2.9% CD8+, 18.5+/-2.2% CD16+, 3.0+/-0.5% CD25+, and 5.5+/-1.8% CD69+. The corresponding proportions in humans were 23.8+/-7.1%, 12.8+/-3.2%, 4.5+/-1.0%, and 2.3+/-1.1%. In contrast to human PBL, less than 1% of baboon lymphocytes expressed CD56, CD57, and CD122 (interleukin [IL]-2Rbeta). Baboon lymphocytes showed NK cytotoxic activity against the human K562 and CEM cell lines, which was comparable to human NK activity. Depletion of baboon CD16+ or CD8+ cells led to dramatic decreases in NK cytotoxicity, and removal of both subsets completely abrogated NK activity. Incubation of baboon lymphocytes with human recombinant IL-2 for 1 week led to the appearance of CD56+ cells (11.3+/-2.8%). Most of the baboon CD56+ cells induced in culture were in S and G2 phases of cell cycle. Both baboon and human IL-2-activated lymphocytes were highly cytotoxic against the human LAK-sensitive cell line Daudi. Depletion of baboon CD8+ but not CD56+ cells significantly decreased LAK activity. These studies revealed differences in the NK system of humans and baboons that should be taken into consideration when analyzing immune responses to allo- and xenotransplantation in baboons.
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PMID:Differential expression of natural killer cell markers: human versus baboon. 893 79