Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3. Although JAK3 is required for proper lymphoid development, the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined. Here, we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3. Although IL-2-induced phosphorylation of IL-2R beta, JAK1, and STAT5 all required the presence of JAK3, IL-4-mediated phosphorylation of JAK1, STAT6, and insulin receptor substrates 1 and 2 did not. However, IL-4-induced effects were clearly improved following JAK3 expression. These data indicate that IL-4 signaling occurs in the absence of of JAK3, but is comparatively inefficient. These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4.
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PMID:Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways. 898 19

Competitive PCR was used to evaluate the expression of cytokine, granzyme B, and chemokine genes in lymph nodes of macaques recently infected with the simian immunodeficiency virus (SIV) pathogenic molecular clone SIVmac239 (n = 16), the nonpathogenic vaccine strain SIVmac239 delta nef (n = 8), and the nonpathogenic molecular clone SIVmac1A11 (n = 8). For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13. The levels of gene induction were equally intense for both viruses despite a lower viral load for SIVmac239 deltanef compared with that for SIVmac239. However, the nature of the cytokine network activation varied with the viral inocula. Primary infection with SIVmac239 was characterized by a higher level of IL-4, IL-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239 delta nef. Thus, infection with nef-deleted SIV was associated with a preferential Th1 versus Th2 pattern of cytokine production. Infection with SIVmac1A11 was characterized by a delayed immune response for all markers tested. The unique patterns of cytokine and chemokine gene expression in lymph nodes correlated nicely with the pathogenic potential of the SIV strains used as well as with differences in their ability to serve as protective vaccines.
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PMID:Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy. 899 46

In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4+ T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti-CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10, a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL-10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients.
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PMID:IL-4 synergizes with IL-10 and anti-CD40 MoAbs to induce B-cell differentiation in patients with common variable immunodeficiency. 904 33

It is supposed that Leishmania infection increases human immunodeficiency virus (HIV) replication in seropositive individuals. Two groups of 9 HIV-infected intravenous drug users each, one group with HIV-Leishmania coinfection (as determined by bone marrow microscopy, culture and an immunofluorescent assay, the other with HIV infection alone, but no evidence of Leishmania coinfection were matched for sex, age, time since first diagnosis of HIV infection, number of AIDS-defining diseases, proportion of patients treated with AZT and months of treatment, CD4/CD8 ratio, beta 2-microglobulin level and HIV p24 antigen positivity rate. IL-4, -6, -10 and -12 and IFN-gamma levels were determined by commercial enzyme immunoassays. The HIV-1 RNA copy number was quantified with the nucleic-acid-sequence-based amplification method (NASBA). The differences between the two groups were highly significant for all markers determined except for IL-12 and IFN-gamma. We found a higher viral load in the patients with HIV-Leishmania coinfection compared to the patients with HIV infection alone (p < 0.009). In 6 HIV-positive individuals without Leishmania coinfection, the HIV-1 RNA copy number was below the detection limit of NASBA (i. e. < 400 copies/100 microliters). Plasma levels of IL-4, -6, and -10 were significantly elevated in the coinfected group (p < 0.0001; p < 0.02, and p < 0.005). The results of our study show that the viral load is increased in patients with HIV-Leishmania coinfection in comparison to the controls. This might be partly due to Th2 immune activation, as demonstrated by higher plasma levels of IL-4, -6 and -10 in HIV-Leishmania-coinfected patients than in HIV-infected individuals.
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PMID:Immunological findings in HIV-Leishmania coinfection. 907 71

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11

Infection of C57BL/6 mice with a mixture of murine leukemia viruses (MuLVs) designated LP-BM5 MuLV leads to a disease characterized by progressive immunodeficiency and lymphoproliferation, known as murine AIDS (MAIDS). The development of MAIDS is associated with increased B-cell lymphoblast proliferation, but there is reason to believe that T-cell function and, particularly, T-cell-derived cytokines may also play a role. We have previously shown that concurrent infection with Leishmania major (which induces a strongly polarized Th1 response in C57BL/6 mice) and LP-BM5 MuLV modulates the disease induced by both infections. Here we show by treatment of mice with anticytokine antibodies that this modulation is largely exerted through the balance of Th1 and Th2 cytokines. Infected mice treated with antibodies to interleukin-4 and interleukin-10 exhibited a delayed development of MAIDS-related pathology and maintained T-cell responsiveness longer than mice treated with control antibody. Gamma interferon induced by coinfection with L. major synergized with anti-IL-4 treatment to inhibit the development of MAIDS pathology. Conversely, treatment with anti-gamma interferon led to a significant increase in splenomegaly and lymphadenopathy and slightly exacerbated loss of T-cell function. These data suggest that the production of Th2-associated cytokines may promote MAIDS pathology, while Th1-associated cytokines may help control the disease.
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PMID:Modulation of murine AIDS-related pathology by concurrent antibody treatment and coinfection with Leishmania major. 909 44

We have engineered recombinant vaccinia virus vectors expressing murine interleukin-7 (IL-7) in order to study the activity of this factor during virus infection. Virus-encoded IL-7 dramatically increased splenic cellularity in infected mice and enhanced the proliferative activity of T cells and their capacity to secrete IL-2 and IL-6, but not IFN-gamma, TNF-alpha or IL-4. Numbers of splenic CD4+ and CD8+ T lymphocytes were elevated two- to threefold. IL-7 also mediated a marked enhancement of both antigen-specific and nonspecific cellular immune activity. Total splenic antiviral cytotoxic T cells (CTL), natural killer (NK), and lymphokine-activated killer cells (LAK) responses were augmented significantly in mice given VV-HA-IL-7 compared with those given control virus, with accelerated clearance of the former. The enhanced antiviral cellular immune activity mediated by IL-7 was critically dependent on IL-2 produced by the host, but occurred independently of IFN-gamma. The ability of IL-7 to induce cellular immune responses in vivo may have applications in antiviral immunotherapy, particularly in cases of immunodeficiency.
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PMID:Interleukin-7 enhances cell-mediated immune responses in vivo in an interleukin-2-dependent manner. 909 26

IL-2 was initially defined as a T lymphocyte growth factor, but recent studies have provided evidence that it may also play a role in regulating T cell differentiation, apoptosis, and tolerance. To examine the contribution of IL-2 to these processes, we have bred a class II-restricted TCR transgene into mice deficient in the alpha-chain of the IL-2R, CD25. We show that in response to Ag, T cells from these mice are unable to use IL-2 and, as a result, are less efficient at traversing the cell cycle, and proliferate less than wild-type cells. Furthermore, CD25 -/- T cells exhibit reduced survival in vitro, even in the presence of costimulatory signals. IL-4 and IL-15, a cytokine related to IL-2, enhance the survival and Ag-induced proliferation of CD25 -/- T cells. Activated CD25 -/- T cells are resistant to Fas-mediated activation-induced cell death (AICD), and this defect cannot be corrected by other cytokines. Therefore, IL-2 plays a unique role in regulating AICD, but has redundant roles in T cell survival and proliferation in vitro. The failure of AICD observed with CD25 -/- T cells may explain the unexpected observation that deficiency of IL-2 or of the alpha- or beta-chain of the IL-2R results not in immunodeficiency, but in autoimmune disease.
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PMID:Functional responses and apoptosis of CD25 (IL-2R alpha)-deficient T cells expressing a transgenic antigen receptor. 910 38

Herpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus which can immortalize human T lymphocytes similar to Epstein-Barr virus immortalization of B cells. The HVS-immortalized T cell lines can be cloned and they remain functional, including susceptibility of CD4 expressing T cells to infection with human immunodeficiency virus type 1 (HIV-1). In this report, we have used five such HVS-transformed CD4-positive T cell clones to reevaluate the role of endogenous interferon gamma (IFN gamma) in HIV-1 replication in T cells. All five clones had similar phenotypes; and four clones constitutively produced IFN gamma and one clone did not. All five clones could be efficiently infected with HIV-1. HIV-1 infection of the IFN gamma-positive cells also upregulated IFN gamma mRNA production and IFN gamma secretion but not production of IL-2 or IL-4. In contrast, infection of IFN gamma-negative cells did not induce IFN gamma, IL-2, or IL-4. Exposure to anti-IFN gamma antibodies after HIV-1 infection significantly reduced virus production and inhibited virus-induced death of IFN gamma-positive cells but had no effect on IFN gamma-negative cells. We conclude that in CD4-positive T lymphocytes immortalized by HVS endogenous IFN gamma does not inhibit HIV-1 but enhances HIV-1 replication and cytolysis. The potential augmenting effects of IFN gamma on HIV-1 replication in CD4-positive T cells recommend caution in a therapeutic use of this cytokine in AIDS.
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PMID:Human immunodeficiency virus type 1 (HIV-1) infection of herpesvirus saimiri-immortalized human CD4-positive T lymphoblastoid cells: evidence of enhanced HIV-1 replication and cytopathic effects caused by endogenous interferon-gamma. 914 96

Altered cytokine transcription might play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection in humans. The infection of rhesus macaques with simian immunodeficiency virus (SIV) provides a relevant animal model for HIV infection. Therefore, we evaluated the cyokine transcription of phytohemagglutinin (PHA)-stimulated lymphocytes in the early phase after infection of four rhesus macaques with pathogenic SIV-mac239. To determine transcription of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6, and IL-10 we established a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). After inoculation with SIV, all monkeys became productively infected and developed an acquired immunodeficiency syndrome (AIDS) like disease. Infection was associated with a proliferation dysfunction of monkey lymphocytes in response to PHA. In addition, a decreasing overall cytokine transcription could be observed during the course of SIV infection. These findings demonstrate that an impairment of the lymphocyte function is associated with a reduced cytokine transcription in the early phase of an immunodeficiency virus infection. The observed differences of cytokine expression might contribute to the impaired immune response of SIV-infected monkeys and HIV-infected humans.
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PMID:Impaired mitogen-driven proliferation and cytokine transcription of lymphocytes from macaques early after simian immunodeficiency virus (SIV) infection. 921 Feb 80


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