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)

Pulmonary involvement has been demonstrated in patients with spastic myelopathy associated with HTLV-I infection (HAM/TSP). Pulmonary lesions in these patients are characterized by T-lymphocytosis and increased level of soluble IL-2 receptor in bronchoalveolar lavage fluid. T-lymphocytes from peripheral blood and bronchoalveolar lavage fluid proliferated spontaneously and released IL-2 and IL-2 receptor when cultured in vitro. Spontaneous proliferation of T-lymphocytes was also found in HTLV-I carriers without myelopathy, but less intensely than in HAM/TSP patients. Interestingly, HTLV-I-infected cells were markedly increased in bronchoalveolar lavage fluid from HAM/TSP patients compared to HTLV-I carriers without myelopathy. These results suggest that T-lymphocyte activation and increased HTLV-I-infected cells play an important role in the pathogenesis of pulmonary involvement in patients with HAM/TSP.
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PMID:[Pathogenesis of T-lymphocyte alveolitis associated with HTLV-I infection]. 163 41

A 66-year-old female suffering from HTLV-1 associated myelopathy (HAM) for more than 30 years was hospitalized because of memorial impairment, deafness, dysarthria, dysphagia, and complete paraplegia. She first noticed stiffness and weakness of the right leg at 35 years of age. Gait disturbance was slowly progressed and complete paraplegia developed 18 years later. Neurological examinations on admission revealed that she was bedridden with decubitus, mental deterioration (pre-dementia of subcortical type), bilateral optic nerve atrophy, severe sensory-neural deafness, dysarthria, complete paraplegia, and marked neurogenic bladder. Laboratory data showed mild normocytic anemia and moderate diabetes mellitus. Anti-HTLV-1 antibody titers in serum and CSF were 78,192X and 1,024X, respectively (PA method). Serum levels of soluble IL-2 receptor was markedly elevated (2,200 U/ml). Peripheral blood lymphocytes showed spontaneous proliferation when cultured for 5 days (3H-thymidine uptake; 45,285 cpm/5 X 10(4) cells). MRI examinations of the spinal cord disclosed a predominant atrophy of lower thoracic cord without any compressive lesions. Brain MRI showed diffuse high intensity lesions of the periventricular area on T2 weighted images. Such abnormalities were predominantly found in fronto-parietal region and were quite similar to those of leuko-ariosis. Single photon emission CT using 123I-iodoamphetamine showed hypoperfusion of cerebral white matter on delayed image. It has been reported that intellectual impairment and brain atrophy are not usually seen in HAM patients. The present case, however, shows that such abnormalities of the central nervous system could occur in HAM patients with a long duration of illness.
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PMID:[A case of HTLV-1 associated myelopathy progressed in course over 30 years]. 189 70

Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM), 5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic and immunohistochemical observations. These T cell responses were also found in asymptomatic carriers, but the responses were not as marked as those of HAM patients. IL-2 activity in the culture supernatants was much higher in HAM patients than in asymptomatic carriers; IL-2 activity correlated well with the intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2 receptors in the cell-free supernatants from HAM patients were markedly increased compared to those from asymptomatic carriers. These results indicate that spontaneous proliferation of T cells is intimately related to HTLV-I infection and is probably due to autocrine or paracrine pathways which involve IL-2 and IL-2 receptor system.
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PMID:Immunological abnormalities in HTLV-I-associated myelopathy: spontaneous release of interleukin-2 and interleukin-2 receptor by peripheral blood lymphocytes. 198 52

A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM/TSP.
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PMID:Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. 236 34

It has been shown that there are pulmonary involvements in patients with HTLV-1-associated myelopathy (HAM). Pulmonary lesions found in HAM are characterized by T-lymphocytosis and increased levels of soluble IL-2 receptor in bronchoalveolar lavage fluid. Peripheral blood lymphocytes from HAM patients proliferated spontaneously when cultured in vitro. Lymphocytes proliferated were positive for CD3 and HLA-DR staining. There were CD4+ cells and CD8+ cells in proliferating T-lymphocytes 5 days after cultivation. Culture supernatants of proliferating cells showed an increased soluble IL-2 receptor. These results suggest that activated T-cells play an important role in developing pulmonary lesions in HAM.
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PMID:[Pathogenesis of pulmonary involvement in HTLV-I-associated myelopathy (HAM): studies on T-cell function]. 261 72

Sera and cerebrospinal fluid (CSF) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were analyzed by Western blotting, and normal human leukocytes were transformed by co-cultivation with HAM patients' leukocytes. The sera and CSF from all HAM patients formed specific bands with HTLV-1 viral proteins, including p19, p24, p28, p32, p40 and p53. After 2-3 weeks of co-cultivation, scattered foci of cell aggregates were noted on macrophage sheets. Surface markers of the transformed cells were OKT3(+), OKT4(+), OKT8(-), IL-2 receptor(+) and EBNA(-). Chromosome analysis showed a normal karyotype. HTLV-1 viral genome was integrated into DNA isolated from transformed cell lines. Electron microscopy revealed type C virus particles in transformed T-cell lines. These results indicate that peripheral leukocytes from HAM patients can transform HTLV-1-negative leukocytes and HAM patients have the potential to acquire adult T-cell leukemia in the future.
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PMID:Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. 288 13

We found unstimulated (spontaneous) peripheral blood lymphocyte (PBL) proliferation significantly increased in 14 patients with human T-lymphotropic virus (HTLV)-I-associated myelopathy (HAM) compared with findings in HTLV-I seropositive non-HAM carriers (N = 8) or HTLV-I seronegative controls (N = 16). The proliferative response to phytohemagglutinin, concanavalin A, or pokeweed mitogen was decreased in the HAM patients. Cell clusters were frequent in cultures of unstimulated PBL from the HAM patients, but much less common in the controls or carriers. This spontaneous PBL proliferation was depressed when adherent-cell populations were depleted from the cultures. IL-2 activity increased in the supernatant of 3-day cultured cells from HAM patients, but not in cultured cells from the controls. Since IL-2 receptor positive cells increased in HAM, this spontaneous PBL proliferation is probably a response to IL-2 through the expression of IL-2 receptors.
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PMID:Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. 289 62

Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.
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PMID:Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals. 791 May 32

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA transcripts encoded from open reading frames (ORFs) I and II of the viral pX region are expressed both in vitro and in infected individuals. The ORF I mRNA encodes the protein p12(I), which has been shown to localize to cellular endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well as bind to the IL-2 receptor beta and gamma chains and the H+ vacuolar ATPase. It is unknown what role p12(I) plays in the viral life cycle. Using an infectious molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12(I), which fails to produce the p12(I) message, we investigated the importance of p12(I) in infected primary cells and in a rabbit model of the infection. ACH.p12(I) was infectious in vitro as shown by viral passage in culture and no qualitative or quantitative differences were noted between ACH and ACH.p12(I) in posttransfection viral antigen production. However, in contrast to ACH, ACH.p12(I) failed to establish persistent infection in vivo as indicated by reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen production in peripheral blood mononuclear cell (PBMC) cultures, and only transient detection of provirus by polymerase chain reaction in PBMC from ACH.p12(I)-inoculated rabbits. These results are the first to show the essential role of HTLV-1 p12(I) in the establishment of persistent viral infection in vivo and suggest potential new targets in antiviral strategies to prevent HTLV-1 infection.
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PMID:Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo. 961 68

A 63-year-old man, whose father died of malignant lymphoma, developed subacutely cauda equina/conus medullaris syndrome progressed over 3 months. Initial radicular pain, ascending motor and sensory paralysis without sacral sparing, vesicorectal dysfunction were similar with signs of spinal dural arteriovenous fistula. However, mild inflammatory signs, raised serum LDH, predominantly of LDH 3, lymphocytic pleocytosis and elevated beta 2 microglobulin in CSF suggested neurolymphomatosis. It was not supported, however, after CSF immunocytochemistry, myelogram, CT, Gd-MRI and Ga scan. Spinal cord/nerve root vascular syndromes of intravascular lymphomatosis (IVL) according to Glass J et al. was suspected because of the unique neurological progression similar to Foix-Alajouanine syndrome, hypoxia without abnormalities in chest X-ray film, response to steroids and raised serum soluble IL-2 receptor. Multiple biopsies were performed with negative results. However, after all muscle biopsy confirmed IVL. The lower spinal irradiation was not effective. But CHOP regimen supplemented by granulocyte colony-stimulating factor (G-CSF) brought about swift neurological improvement and protection from late complications. Self-limiting polyneuropathy emerged during the biweekly CHOP therapy, 6 courses for 12 weeks. Eventually he was neurologically improving 10 months after the chemotherapy and adrenal enlargement, which was possibly of metastasis, was only against complete remission. This case was good outcome by biweekly CHOP using G-CSF when compared with very high mortality in reported IVL cases besides vincristine neurotoxicity under compromised blood-brain/nerve barrier due to IVL might affect the functional recovery. This case with IVL implied raised soluble IL-2 receptor and progressive cauda equina syndrome/ascending myelopathy as diagnostic clues, and efficiency of muscle biopsy to confirm IVL.
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PMID:[A 63-year-old man with progressive cauda equina/conus medullaris syndrome]. 998 61


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