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)

The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma-Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma-irradiation on the phenotypic and functional reconstitution of helper T-cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide "help" for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.
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PMID:Peripheral lymph node helper T-cell recovery after syngeneic bone marrow transplantation in mice prepared with either gamma-irradiation or busulfan. 252 72

CD8+ cells from long-term survivors [LTS; infected with human immunodeficiency virus (HIV) for 10 or more years and having CD4+ cell counts of > or = 500 cells per microliters] have a 3-fold greater ability to suppress HIV replication than do CD8+ cells from patients who have progressed to disease (progressors) during the same time period. A change in the pattern of cytokines produced in the host from those that typically favor cell-mediated immunity (T helper 1, TH1 or type 1) to those that down-regulate it (T helper 2, TH2 or type 2) was investigated as a cause of this reduced CD8+ cell anti-HIV function. Treatment of CD8+ cells from LTS with the TH1 cytokine interleukin (IL)-2 enhanced their anti-HIV activity, whereas exposure of these cells to TH2 cytokines IL-4 or IL-10 reduced their ability to suppress HIV replication and to produce IL-2. IL-2 could prevent and reverse the inhibitory effects of IL-4 and IL-10. Moreover, prolonged exposure of CD8+ cells from some progressors to IL-2 improved the ability of these cells to suppress HIV replication. These observations support previous findings suggesting that strong CD8+ cell responses play an important role in maintaining an asymptomatic state in HIV infection. The data suggest that the loss of CD8+ cell suppression of HIV replication associated with disease progression results from a shift in cytokine production within the infected host from a TH1 to a TH2 pattern. Modulation of these cytokines could provide benefit to HIV-infected individuals by improving their CD8+ cell anti-HIV activity.
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PMID:Effects of TH1 and TH2 cytokines on CD8+ cell response against human immunodeficiency virus: implications for long-term survival. 747 52

We report a new approach in peptide vaccine strategy based on combinatorial synthesis. A library of 7.5 x 10(5) related peptides, termed mixotope, was derived from the sequence of the third hypervariable domain (V3 loop) of the human immunodeficiency virus (HIV) envelope protein. This preparation induced a strong immune response in all syngeneic and outbred rodents tested. The response directed against the mixotope included antibodies, CD4+ T helper cells (TH1 and TH2) and CD8+ T cells. In rodents immunized with the mixotope, the T cell response directed against individual V3 peptide sequences (BRU, MN, RF, SF2, and ELI) as measured by T cell proliferation and interleukin (IL)-2 production, was found to be major histocompatibility complex haplotype-dependent. However, additional experiments performed in mice indicated that selectivity was less restrictive when using IL-3 secretion to explore T cell activation. This combinatorial antigen could be considered as a series of agretopic motifs framing a multiplicity of closely related epitopes for T cell recognition and able to elicit a T cell and B cell repertoire. This new construct may therefore provide a basis for the design of future vaccine strategies.
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PMID:The mixotope: a combinatorial peptide library as a T cell and B cell immunogen. 795 71

The aim of the present study was to determine the profile of immune responsiveness that differentiates patients with tuberculosis (TB) from healthy tuberculin-positive controls. Forty-five patients with pulmonary TB and 16 healthy tuberculin-positive controls, all human immunodeficiency virus negative, were studied. Patients had decreased reactivity to tuberculin, diminished proliferative response to purified protein derivative (PPD), lower concentrations of interleukin-2 (IL-2) and gamma interferon in PPD-stimulated cultures, no increase in the percentage of gamma/delta cells in PPD-stimulated cultures, and higher immunoglobulin G antimycobacterial antibodies compared with control subjects. Furthermore, controls exhibited decreased production of IL-4 by PPD-stimulated cells. Multivariate discriminant and factor analyses demonstrated divergent patterns of immune reactivity against mycobacterial antigens. The association of IL-4 and immunoglobulin G antibody levels in patients, in contrast to the high reactivity to tuberculin, increased proliferation to PPD, and higher levels of IL-2 and gamma interferon observed in healthy controls suggested that most TB patients exhibit a TH2 pattern of immune responsiveness while tuberculin-positive healthy individuals have a TH1 pattern.
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PMID:Immune responsiveness and lymphokine production in patients with tuberculosis and healthy controls. 796 Jan 52

We evaluated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in peripheral blood lymphocytes (PBLs) from six patients with common variable immunodeficiency (CVID). IL-2 production and IFN-gamma concentrations were not reduced in these patients. As the production of IL-2 and IFN-gamma secreted from TH1 clones was within the normal range in patients with CVID, we concluded that TH1 function was normal in these patients. Our previous report showed B-cell dysfunction in CVID patients. Therefore, we concluded that the immune defect in these patients is caused by B-cell dysfunction rather than T-cell dysfunction.
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PMID:Interleukin-2 and interferon-gamma production by peripheral blood lymphocytes of patients with common variable immunodeficiency. 798 81

The pathogenesis of several infectious diseases is frequently related not only to their etiological agents of viral, bacterial, or parasitic nature, but also to the host immune response. Both inflammatory responses and specific immune responses to the invading microorganisms are controlled by complex networks of intercellular signalling molecules, namely cytokines. This rapidly growing family of mediators includes lymphokines, interleukins, and molecules such as tumor necrosis factors and interferons. Patterns of cytokine production from antigen- or allergen-specific T lymphocytic cell clones have been identified, firstly in animal models and subsequently in man, and are commonly referred to as TH0, TH1, and TH2 profiles. The predominance of one of these profiles strongly influences the type of immune response (humoral versus cellular) and, at least in some experimental models, whether the immune response is protective or harmful. This is most convincingly demonstrated in models of parasitic diseases, but has also been hypothesized to be involved in the pathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Earlier studies on human immunodeficiency virus infection revealed that the replicative capacity of this retrovirus, like the herpes viruses, is strongly influenced by the cytokine milieu of infected cells. Transcriptional and post-transcriptional regulation of human immunodeficiency virus expression by human cytokines are examples of the complex interdigitation of viruses with the host immune system.
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PMID:Cytokines in the acquired immunodeficiency syndrome and other infectious diseases. 856 74

Nonhuman primates naturally infected with simian immunodeficiency virus (SIV), while maintaining chronic viremia, do not develop any disease associated with lentiviral infection. Thus they provide a unique model to define the mechanism(s) by which they remain infected but disease-resistant. The purpose of this article is to summarize our current knowledge of the virological and immunological studies that have been performed in sooty mangabeys naturally infected with SIVsmm and in disease-susceptible rhesus macaques experimentally infected with SIVsmm. Data on virological studies demonstrate that the naturally infected sooty mangabeys are infected predominantly with SIV that have nef sequences distinct from those shown to cause disease in the inappropriate host, a factor which may contribute to disease resistance. Hyperimmunization with a variety of antigens or chronic infection contributes to accelerated disease and death in rhesus macaques if hyperimmunizations are initiated at the time of SIV infection, whereas similar hyperimmunization and chronic infection do not lead to disease in naturally infected seropositive sooty mangabeys. However, in both species infected with SIV, hyperimmunization leads to increased virus load, suggesting that virus load per se cannot account for disease, at least in naturally infected nonhuman primates. Immunological studies concerning changes in subsets of T cells, based on cytokine profile (TH0/TH1/TH2), showed that whereas rhesus macaques early post SIV infection show a dominant TH1 profile, this profile rapidly changes to TH0. On the other hand, mangabeys continuously demonstrate a TH2-like profile. Studies also showed a high frequency of in vivo-activated cells in the peripheral blood of SIV-infected rhesus macaques and mangabeys. Of interest, however, is the finding of a similar level of in vivo-activated cells from ELISA seronegative mangabeys. Although cells from SIV-infected mangabeys fail to show increased levels of apoptotic cells following incubation with immobilized anti-CD3, PBMC from rhesus macaques at varying time intervals do show increased levels of apoptotic cells, an increase which is predominantly seen in CD8+ T cells and is unrelated to levels of viremia. Sooty mangabeys maintain a high frequency of CD8+ T cells that regulate virus replication throughout their lifetime, a frequency that develops prior to ELISA-based seroconversion, whereas rhesus macaques only show a frequency of CD8+ T cells high enough to regulate virus replication shortly post infection, and this regulatory function is gradually lost prior to CD8+ cell loss and death. HIV and SIV infection do have profound effects on the expression of a number of costimulatory and adhesion molecules. There appear to be differences in the nature of the intracellular phosphorylated proteins in cells from activated rhesus macaques and mangabeys. We believe that careful studies of the detailed mechanisms of the issues described above may provide an understanding of the constellation of virological and immunological mechanisms responsible for the disease-resistant state of naturally infected sooty mangabeys. These findings can be employed for evaluating a nonvirus sterilizing form of SIV/HIV vaccines.
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PMID:Immunological and virological studies of natural SIV infection of disease-resistant nonhuman primates. 881 46

Infection with the human immunodeficiency virus (HIV) is accompanied by a decrease in CD4+ T cell numbers and the ultimate disruption of immunological functions. In sera of infected patients, elevated levels of interferon-gamma are detected, which is indicative of an activated TH1-type immune response. T-cell-derived interferon-gamma leads to the expression of various proinflammatory cytokines and enhanced macrophage capacity to secrete reactive oxygen intermediates. In addition, interferon-gamma is the major stimulator for the biosynthesis of neopterin and its reduced form, 7,8-dihydroneopterin. Neopterin is known as a sensitive immune activation marker in clinical laboratory diagnosis. Recent data implied a potential role of neopterin derivatives in oxygen free-radical-mediated processes, e.g. high concentrations of 7,8-dihydroneopterin were found to interfere with the oxidant-antioxidant balance, and may lead to apoptosis of human cells. In addition, 7,8-dihydroneopterin was found to be effective in the activation of redox-sensitive transcription factors and in the induction of HIV-1 gene expression. In this commentary, we describe our current view as to how neopterin derivatives, in concert with cytokines and reactive oxygen intermediates, may lead the way to the final destruction of the cellular immune system.
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PMID:Chronic immune stimulation, oxidative stress, and apoptosis in HIV infection. 911 96

Omenn syndrome comprises a rare form of combined immunodeficiency with TH2-type features of eosinophilia and elevated IgE. Previous studies have led to reports of restricted heterogeneity in the T lymphocyte repertoire, and in vitro cloned T lymphocytes have been shown to produce IL-4 and IL-5. We hypothesized that (1) T cell receptor beta V(D)J DNA sequence analysis would confirm and further define the putative restricted heterogeneity, and (2) increased production of IL-4 and IL-5 should be found in nonstimulated T lymphocytes, if the molecular pathogenesis of Omenn syndrome is an uncontrolled TH2 state. We report the results of molecular analyses of T lymphocytes from an untreated 3-month-old patient. Oligoclonal T cell receptor beta variable gene usage was found. Sequence analysis revealed sets of identical V(D)J sequences, each in-frame, with apparently normal N-diversification and no obvious antigen combining site motif. From fresh, nonstimulated lymphocytes, proinflammatory TH1 cytokines could be detected, but TH2 cytokines could not, so that a simple TH1/TH2 paradigm cannot explain the eosinophilia and elevated IgE in Omenn syndrome. Our studies fully document for the first time at the molecular level that clonally expanded populations of T lymphocytes are present in Omenn syndrome.
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PMID:Oligoclonal expansion of CD45RO+ T lymphocytes in Omenn syndrome. 925 71

Studies on the development and function of CD4+ TH1 and TH2 cells during the progression to AIDS may increase the understanding of AIDS pathogenesis. The preferential replication of human immunodeficiency virus (HIV) in either TH1 or TH2 cells could alter the delicate balance of the immune response. TH1 (gamma interferon [IFN-gamma] positive, interleukin-4 [IL-4] and IL-5 negative) and TH2 (IFN-gamma negative, IL-4 and IL-5 positive) clones, developed from several healthy donors, pedigreed by reverse transcriptase PCR (RT-PCR) and enzyme linked immunosorbent assay have similar levels of cell surface expression of CD4 and several chemokine receptor cofactors necessary for viral entry. After activation by specific antigens and infection with T-cell-tropic strains of HIV type 1 (HIV-1), TH1 and TH2 clones showed similar levels of viral entry and reverse transcription. At days 3 through 14 postinfection, HIV replicated to similar levels in several TH1 and TH2 clones as measured by release of HIV p24 and total number of copies of gag RNA/total cell RNA as measured by RT-PCR. When values were normalized for viable cell number in three clones of each type, there was up to twofold more HIV RNA in TH1 than TH2 cells. In addition, several primary monocytotropic HIV-1 strains were able to replicate to similar levels in TH1 and TH2 cells. These studies suggest that the importance of TH1 and TH2 subsets in AIDS pathogenesis transcends clonal differences in their ability to support HIV replication.
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PMID:Similar levels of human immunodeficiency virus type 1 replication in human TH1 and TH2 clones. 957 96


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