Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human T-cell leukemia virus type I (HTLV-I) encodes a trans-activator protein p40x which positively regulates transcription of the viral RNA as well as interleukin-2 and its receptor genes. We placed a cDNA coding for p40x in baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) expression vectors. Infection of BmN cells derived from an insect, B. mori (silkworm), with a recombinant virus led to the production of soluble p40x. The biological activity of the recombinant p40x was demonstrated by introducing the protein into intact NIH 3T3 cells that had been selected for genomic integration of HTLV-I LTR connected with the CAT gene. Immunocytochemical and cell fractionation analyses showed the localization of p40x in both the cytoplasmic and nuclear fractions of BmN cells. Analyses of 32P-labeled proteins of BmN cells by cell fractionation and subsequent immunoprecipitation revealed that the p40x present in each subcellular fraction was phosphorylated. The post-translational modification was inhibited by the addition of a protein kinase inhibitor K252a during the metabolic labeling of BmN cells. Phosphoamino acid analysis indicated that the phosphorylation occurred on serine residues of p40x.
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PMID:Evidence for phosphorylation of trans-activator p40x of human T-cell leukemia virus type I produced in insect cells with a baculovirus expression vector. 305 77

Recombinant vaccinia viruses have been proposed as live vaccines against a variety of infectious diseases, including AIDS (acquired immune deficiency syndrome). Objections have been concerned primarily with side effects of the vaccinia virus vector itself. Recently it has been shown that inactivation of the vaccinia virus thymidine kinase gene or deletion of certain other non-essential genes is associated with a marked reduction in pathogenicity. Nevertheless, the ability of vaccinia virus to produce a progressive infection in immunodeficient individuals remains a most serious problem. Indeed, an incident of this type in a vaccinated man seropositive for human immunodeficiency virus was recently reported. We have used immunodeficient athymic nude mice to establish a model of disseminated vaccinia virus infection, and to demonstrate a novel approach to virus attenuation which involves insertion of a gene encoding human interleukin-2 into the genome of vaccinia virus vectors.
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PMID:Prevention of vaccinia virus infection in immunodeficient mice by vector-directed IL-2 expression. 311 19

Evidence is summarized to suggest that both CD4 and CD8 T cells and both helper and cytolytic T cell functions are involved in protective immunity to infection with the intracellular bacterium, Listeria monocytogenes. This suggestion is based on the following findings obtained with T cell lines and clones from L. monocytogenes infected mice: L3T4+ (CD4) T cells produce multiple lymphokines after antigen stimulation in vitro; Lyt2+ (CD8) T cells lyse L. monocytogenes primed macrophages; L3T4+ (CD4) T cells also lyse L. monocytogenes primed macrophages provided the latter express Ia-molecules; Lyt2+ (CD8) T cells secret Interferon-gamma provided that exogenous Interleukin-2 is supplied. Furthermore, both L3T4+ (CD4) and Lyt2+ (CD8) T cell lines can confer a certain degree of adoptive protection upon naive recipient mice.
Infection 1988
PMID:Listeria monocytogenes specific T-cell lines and clones. 313 85

Soluble glucan, a beta-1,3-linked polyglucose, is a biologic response modifier effective in the therapy of experimental neoplasia, infectious diseases and immunosuppression. Interleukin-1 (IL-1) and interleukin-2 (IL-2) are endogenous immunomodulators which are essential for effective immune responsiveness. In view of its broad spectrum of immunobiological activity, the ability of glucan to enhance the production of IL-1 and IL-2 was evaluated. Splenic IL-1 and IL-2 secretion as well as plasma IL-1 and IL-2 levels were determined in Sprague-Dawley rats receiving glucan (100 mg/kg, i.p.) at intervals ranging from 12 days to 1 h prior to collection of splenocytes and plasma. Glucan (100 mg/kg) was also injected either s.c., i.p. or i.v. on days -4, -3 and -2 prior to harvesting splenocytes on day 0. Splenic macrophage IL-1 production was initially elevated 12 h following glucan injection and was maintained for a 5 day period. IL-2 secretion by splenic lymphocytes was enhanced 6 h post-glucan and remained elevated for an additional 9 days. Plasma IL-1 activity was elevated 12 h post-injection, while IL-2 activity in plasma was enhanced at 1 h post-glucan. Peak IL-1 and IL-2 activity in plasma occurred 9 and 12 days, respectively, following glucan administration. With regard to route of administration, IV glucan was most effective in inducing lymphokine production. This study demonstrates that: (1) glucan will enhance IL-1 and IL-2 production and (2) elevations in lymphokine production can be maintained up to 12 days post-glucan.
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PMID:Enhancement of interleukin-1 and interleukin-2 production by soluble glucan. 349 13

Not all cancer-bearing hosts respond to interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cell immunotherapy. We wished to determine if modification of the host could change the immunotherapeutic effects. Alloimmunization of the host was used to study the suppression observed when LAK cells were generated in the presence of cytotoxic T lymphocytes (CTL). If C57BL/6 (BL/6, H-2b) mice were given P815 (H-2d) tumor prior to syngeneic tumor challenge, the immunotherapeutic effects of IL-2 were lost. Cells taken from mixed lymphocyte culture and incubated 3 days in IL-2 showed a reduced capability of generating LAK. However, their cytotoxicity toward an alloimmunogeneic target was markedly increased by 3 days of incubation in IL-2. In mixing experiments alloimmune cells from in vitro culture were markedly inhibitory to normal splenocytes in the generation of LAK cell cytotoxicity; they also interfered with the maintenance of LAK cell cytotoxicity. A T cell was responsible for the suppressive effects on LAK generation because suppression was abrogated by treatment of alloimmune cells with anti-T serum plus complement. The cytotoxic T cell did not lyse the LAK cell. If IL-2 was serially diluted and incubated with CTLs, the IL-2 titer was substantially reduced by 72 h incubation. If supernatants from CTLs were added to serially diluted IL-2, the IL-2 titer increased; this suggested that a soluble suppressor factor produced by CTLs did not cause the diminished IL-2 plus LAK effects. These in vitro experiments suggest that CTLs compete with normal lymphocytes or LAK cells for IL-2 and thereby suppress LAK cell responses. These studies are important in attempting to elucidate the role the host's immune system may play in IL-2 plus LAK immunotherapy of cancer or infectious disease processes.
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PMID:Inhibitory effects of alloimmune T cells on the generation of cytolytic responses of lymphokine-activated killer cells. 349 12

AIDS is caused by a newly recognised virus (human immunodeficiency virus; HIV) which induces a profound defect in cellular immune function associated with increased susceptibility to opportunistic infections and certain malignancies. The clinical presentation of HIV ranges from asymptomatic infection to severe immunodeficiency manifesting as severe life-threatening infectious diseases or malignancies. While major research efforts are being directed toward development of vaccine and discovery of effective antiretroviral drugs, clinicians are faced with AIDS patients with multiple and complicated medical problems including opportunistic infections and certain malignancies. Currently, efforts are directed toward early diagnosis, treatment, and prevention of recurrence of these opportunistic infections. The current approaches are reviewed in this article. Major recent developments in AIDS research include the isolation of the HIV on culture and the availability of the antibody test. Aside from vaccine and antiretroviral drugs, other measures that may be of benefit in the treatment of AIDS patients are immunological enhancement and reconstitution. Several studies are underway to evaluate antiviral agents in the treatment of HIV infection. Those undergoing clinical trial include suramin, ribavirin, antimoniotungstate, phosphonoformate and azidothymidine. Immune enhancers that have been used include alpha- and gamma-interferon and interleukin-2. HLA-matched lymphocyte transfusions and bone marrow transplantations have been used alone and in combination to replace the AIDS patient's defective immune system.
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PMID:Management of infectious and immunological complications of acquired immunodeficiency syndrome (AIDS). Current and future prospects. 354 66

Herpesvirus saimiri (HVS) has recently been shown to immortalize human CD4+ and CD8+ T cells expressing T-cell receptor alpha beta (TCR-alpha beta) with the maintenance of their original phenotypes and functional properties. However, the immortalization of human T cells expressing TCR-gamma delta by HVS has not been successful. Here we report that HVS can also infect and immortalize human T cells expressing TCR-gamma delta. Two human TCR-gamma delta+ T-cell clones, which continuously proliferated in interleukin-2-containing culture medium without any exogenous stimulation or addition of feeder cells for more than 8 months, were established by HVS infection. Morphologically, the HVS-transformed TCR-gamma delta+ T-cell clones were granular lymphocytes which exhibited wide-range HLA-unrestricted cytotoxicity as untransformed TCR-gamma delta+ T cells. Their phenotypes and cytotoxic activities were not altered during long-term culture. The immortalization of human TCR-gamma delta+ T cells by HVS infection would be useful for functional analysis of this lymphocyte population, which is believed to play an important role in protection against various infectious diseases.
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PMID:Immortalization of human T cells expressing T-cell receptor gamma delta by herpesvirus saimiri. 749 32

Infection of CMS5 tumor cells with retroviral constructs containing interleukin-2 (IL-2) cDNA and selection in medium supplemented with G418 resulted in the isolation of clones which secreted IL-2. Whereas injection of parental tumor cells resulted in progressive tumor growth, tumor cells secreting high levels of IL-2 were rejected. Furthermore, in animals vaccinated with IL-2-secreting cells, the immunosuppression associated with the inoculation of parental tumor cells did not develop, and these animals resisted a challenge with viable tumor cells. To better understand the functional differences in the anti-tumor responses of immune and tumor-bearing mice which are at the basis for these diverse responses, we used an in vitro model to analyze interactions between splenic lymphocytes and tumor cells. Spleen cells isolated from either tumor-bearing or immune mice proliferated vigorously when cultured alone for 6 days, but much less in the presence of parental tumor cells. This effect could not be transferred with supernatant from tumor cell lines. Spleen cells from tumor-bearing mice remained unresponsive, while those from immune mice proliferated well in response to IL-2-secreting tumor cells. Only spleen cells from immune animals were able to develop cytotoxicity against CMS5 cells following in vitro restimulation. These results are consistent with the interpretation that exposure to parental tumor cells inhibited cell-mediated anti-tumor responses by a mechanism that involved cell-to-cell contact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vaccination with IL-2-secreting tumor cells stimulates the generation of IL-2-responsive T cells and prevents the development of unresponsiveness. 762 Dec 37

Kakkon-to is one of the representative traditional herb medicines (Kampo formulae) and has been used historically for the treatment of infectious diseases in China and Japan. The efficacy of this preparation was characterised using a cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for human viral infection. Kakkon-to at a dose corresponding to human use reduced significantly the mortality of HSV-1-infected mice and localised skin lesions. Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly stronger in treated mice than in untreated mice. However, no histopathological difference was noted in the skin lesions between treated and untreated mice except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1 in vitro. Natural killer cell activity, natural cytotoxic killer cell activity, and the population of T-cell subsets in spleen cells of infected mice were not affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV-1 antibody production, nor increased cytokine levels such as interleukin-1 alpha, interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice, which may have caused localisation of skin lesions and reduction in the mortality of treated mice.
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PMID:Efficacy of kakkon-to, a traditional herb medicine, in herpes simplex virus type 1 infection in mice. 762 3

Feline immunodeficiency virus (FIV) infection in the cat is similar to human immunodeficiency virus type 1 infection in causing a selective reduction in CD4+ cell numbers, leading to inversion of the CD4+/CD8+ ratio. To determine whether FIV, similar to human immunodeficiency virus type 1, has a tropism for CD4+ cells, we examined the in vitro and in vivo susceptibilities of feline lymphocyte subpopulations to FIV infection. Infection of interleukin-2-dependent CD4+ or CD8+ lymphocyte cultures with the NCSU1 isolate of FIV (FIV-NCSU1) resulted in syncytium formation, cell death, and Mg(2+)-dependent reverse transcriptase (RT) activity in both cases. Monoclonal antibodies to feline lymphocyte subsets were used to sort peripheral blood mononuclear cells from FIV-infected cats into highly (> 95%) purified CD4+ cell, CD8+ cell, immunoglobulin-positive (Ig+) cell, and monocyte subpopulations. The mononuclear cell subpopulations were analyzed for FIV provirus by polymerase chain reaction and Southern blot analysis and for virus expression by RT activity. All 16 cats infected with FIV-NCSU1 demonstrated FIV provirus in CD4+ cell-, CD8+ cell-, and Ig+ cell-enriched lymphocyte populations. Southern blot detection of amplified gag gene sequences and limiting-cell-dilution polymerase chain reaction analysis indicated that Ig+ cells carried a higher FIV provirus burden in chronically (> or = 1-year) infected cats than either CD4+ or CD8+ cells. In contrast, CD4+ cells carried the greatest provirus burden in acutely (2- to 4-week) infected cats. FIV provirus was detected in monocytes from only 1 of 10 cats with asymptomatic infection. Addition of culture supernatants from enriched CD4+, CD8+, and Ig+ cells from FIV-infected cats to an FIV-susceptible CD4+ lymphocyte culture resulted in syncytium formation, cell death, and RT activity. Infection of Ig+ cells is not unique to FIV-NCSU1, as lymphocyte subpopulations from other cats with natural infections and cats infected with the Petaluma or Mount Airy isolate of FIV demonstrated a similar distribution of FIV provirus and RT activity. These data suggest that FIV possesses a broad tropism for peripheral blood mononuclear cells and that an Ig+ cell may serve as a major reservoir for the virus in chronically infected cats.
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PMID:In vivo lymphocyte tropism of feline immunodeficiency virus. 768 19


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