Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples. Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome. Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.
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PMID:Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. 131 17

To verify the physiological role of the pore-forming protein perforin in vivo, its expression in subpopulations of human peripheral blood lymphocytes was examined by immunocytochemical staining and their cytolytic potentials compared. In addition to NK cells and gamma delta T cells, which uniformly expressed abundant perforin in their cytoplasmic granules, only a small subpopulation of CD8+ alpha beta T cells contained perforin, namely the CD11b+ subset. However, in vitro activation with an anti-CD3 antibody and IL-2 induced perforin expression in approximately 50% of the CD8+CD11b- T cells and also in a small subset of CD4+ T cells. A distribution of perforin in CD8+ and CD4+ T cells, similar to in vitro activated T cells, was observed in fresh peripheral blood lymphocytes from infectious mononucleosis patients. In all instances, the expression of perforin correlated with the cytolytic potential of these subpopulations. The results strongly suggest that perforin plays a role in the manifestation of cytotoxic activity in vivo.
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PMID:Expression of perforin and cytolytic potential of human peripheral blood lymphocyte subpopulations. 135 28

The transient T cell anergy associated with acute infectious mononucleosis (IM) caused by the Epstein-Barr virus has been analysed in a sample of 14 IM children. Peripheral blood mononuclear cells (PBMC) obtained from IM patients showed a significant specific impairment in their proliferative response to both phytohaemagglutinin (PHA; P less than 0.05) and to an anti-CD3 MoAb (P less than 0.001), although both responses reached normal control levels by addition of a submitogenic dose of either phorbol myristate acetate (PMA) or recombinant IL-2 (rIL-2). In contrast, activation signals delivered through other surface molecules (CD2, CD28) or other transmembrane pathways (PMA plus a calcium ionophore) elicited normal or high proliferative responses in most IM PBMC. In a group of five patients tested, the synthesis of IL-2 by IM PBMC in the presence of PMA was impaired when PHA or anti-CD3 was used as stimulus, but it reached normal levels with anti-CD2 or ionophore. Lastly, PHA failed to induce IL-2 alpha receptor (IL-2R alpha) expression in IM PBMC from four tested patients, but the presence of PMA completely corrected this defect. Taken together, these results strongly suggest that the T cell anergy associated with acute IM is due to a T cell receptor (TCR)-specific impairment in the induction of genes involved in T cell proliferation (including those coding for IL-2 and IL-2R alpha) upon membrane signalling to otherwise normal T lymphocytes, since CD2, CD28 and certain transmembrane activation pathways are uncoupled from CD3 in these particular pathological conditions (and perhaps in most in vivo situations). This and other similar experimental approaches to transient secondary immunodeficiencies may help to unravel the physiopathological role of different surface molecules in T cell activation.
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PMID:T lymphocyte anergy during acute infectious mononucleosis is restricted to the clonotypic receptor activation pathway. 162 27

Killer cell activities were analysed in a 16-month-old boy with a sporadic form of fatal Epstein-Barr virus (EBV) infection, and compared with those in three patients with acute infectious mononucleosis (IM). We used spontaneously EBV-transformed autologous lymphoblastoid B cell lines (LCL) as target cells, because the results obtained with such targets can be expected to reflect most accurately the killer-versus-target reaction in vivo. The patient's fresh peripheral blood mononuclear cells (PBMC) had relatively high natural killer (NK) cell activity against K562 cells (128% of the control value), but they did not kill his autologous LCL. The patient's PBMC, unlike PBMC of acute IM, showed no cytotoxicity against Raji cells and autologous LCL after 5 days' culture in the presence of recombinant interleukin 2 (rIL-2), indicating defective generation of lymphokine-activated killer (LAK) cells. The patient's PBMC, unlike PBMC of acute IM, also could not induce cytotoxicity against autologous LCL when cocultured with mitomycin C-treated respective autologous LCL for 7 days. The addition of rIL-2 to the culture significantly restored their ability to generate cytotoxic T lymphocytes (CTL) against his LCL: the percent cytotoxicity value rose from 3.0% to 37.7%. With respect to this, the endogenous IL-2 production by the patient's PBMC was deficient. These results suggest that the defective EBV-selective CTL generation was due to deficient IL-2 production. The failure of the killer cells to eliminate EBV-infected cells seems to have been responsible for the patient's unusual course after primary EBV infection.
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PMID:Defective generation of killer cells against spontaneously Epstein-Barr virus (EBV)-transformed autologous B cells in a fatal EBV infection. 282 Jun 33

The cytotoxic T-cell response induced by primary Epstein-Barr virus (EBV) infection and detectable in the blood of infectious mononucleosis (IM) patients shows several unusual features when tested in in vitro assays. Lysis of EBV-transformed target lines occurs with no apparent HLA restriction, and the putative EBV specificity of the response has been seriously questioned. In the present work we show that the primary T-cell response in IM is polyclonal and indeed does contain a virus-specific HLA class I antigen-restricted component, which can be selectively expanded in vitro in the presence of appropriate stimulator cells and IL-2. This allows functional analysis of the virus-specific component of the response in the absence of co-resident reactivities. Studies on blood samples taken from individuals in the acute phase of IM and again post-convalescence suggest that functionally similar populations of HLA class I-restricted cytotoxic T cells are involved in the control of both the primary and persistent phase of EBV infection.
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PMID:In vitro expansion of Epstein-Barr virus-specific HLA-restricted cytotoxic T cells direct from the blood of infectious mononucleosis patients. 282 28

Somatic cell hybridization was utilized to produce hybrids with surface receptors that would pertain directly to those expressed in vivo during Epstein-Barr virus (EBV) infection. Lymphocytes were obtained during acute infectious mononucleosis (IM) and fused to a double mutant of the JM human T-lymphoma cell lines. Hybrid cells that reacted with autologous EBV-infected lymphoblasts were detected by the release of Interleukin-2 into the culture medium. Reactive hybridomas also released IL-2 following coculture with allogeneic EBV-infected cells when those cells shared HLA-DR antigens of the primary parental cells. In contrast, stimulator cells with no shared HLA-DR or without evidence of EBV infection never induced IL-2 release. These results suggest the existence of a population of T cells that arise during acute IM and could account for the known proliferative phase of the disease. The requirements of IL-2 stimulation are currently under study using this system.
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PMID:Characterization of Epstein-Barr virus-specific T-cell hybridomas derived from infectious mononucleosis. 299 57

Epstein-Barr virus (EBV) has a marked tropism for cells of the immune system, and infection can result in profound immunomodulatory effects. In order to examine the role of cytokines during the acute phase of infectious mononucleosis, we studied the levels of different interleukins (ILs), interferons (IFNs), and the soluble IL-2 receptor (sIL-2R) in serum samples of 20 patients. We found elevated levels of IL-2, IL-6, sIL-2R, and IFN-gamma. Whereas the peak of IL-2 and IL-6 concentration occurred during the first week (P < 0.01), the largest amounts of sIL-2R were measured during the second week (P < 0.01). IFN-gamma levels were only enhanced during the first week. In addition, we investigated the ability to produce cytokines in response to mitogenic stimulation in a whole-blood assay of 11 patients compared with healthy blood donors. In the whole-blood assay of patients compared with controls after stimulation with lipopolysaccharide, we measured more than 10-fold elevated levels of tumor necrosis factor alpha (P < 0.01), 3-fold elevated levels of IL-1 beta (P < 0.01), and about 2-fold increased amounts of IL-6 (P < 0.01). A significant enhancement in sIL-2R and IFN-gamma concentration was found in the assay after stimulation with phytohemagglutinin after 24 h of incubation (P < 0.01). Collectively, our data seem to indicate that monocytes are strongly activated during infectious mononucleosis. Monocytes and monocyte-derived factors may play an important role in the pathogenesis of infectious mononucleosis and, together with T lymphocytes, may be partly responsible for clinical symptoms.
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PMID:Cytokine production in a whole-blood assay after Epstein-Barr virus infection in vivo. 769 31

Accumulating data indicate that cytokines, peptides involved in regulation of both physiological and pathological immune responses, are produced predominantly at the site of local antigen stimulation. Cytokine-producing cells were detected at the protein level in human tonsil tissue obtained from children with recurrent tonsillitis or infectious mononucleosis (IM). Concomitant production of 19 different human cytokines, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta 1-3 (TGF-beta 1-3), was identified at a single-cell level by indirect immunohistochemical staining procedures and use of carefully selected cytokine-specific antibodies (Ab). Fresh frozen sections were fixed with 4% paraformaldehyde and permeabilized by 0.1% saponin treatment, eluting cholesterol from the cell-surface membrane and the Golgi complex. The intracellular localization of all cytokines, except IL-1 and IL-1ra, was demonstrated by a characteristic local cytoplasmic perinuclear configuration in producer cells. In addition, the immunoreactivity for certain cytokines (IL-2, IL-4, IL-5, G-CSF and GM-CSF) was expressed on the cell membranes and extended over a large extracellular area encompassing the producer cell. Localization of the cytokine to the Golgi organelle was established by co-staining with a monoclonal antibody (mAb) specific to the Golgi complex. Both the extra- and intracellular cytokine staining reactions could be blocked by preincubation of the cytokine-specific Ab with the corresponding purified natural or recombinant cytokine. A complex cytokine pattern was established in both groups studied, where most T-helper type 1 (Th1) and Th2 lymphokines were expressed in the tonsils but at different frequencies and localizations. Cells expressing IL-4, IL-5, IL-10 and IL-13, (Th2 response) were evident at higher frequencies in recurrent tonsillitis compared to sections from IM, which were associated with a more pronounced IL-2, IFN-gamma and TNF-beta expression.
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PMID:Concomitant in vivo production of 19 different cytokines in human tonsils. 782 61

AIDS typically consists of three phases: (1) an acute, infectious mononucleosis-like syndrome followed by (2) a prolonged asymptomatic stage ending in (3) the appearance of frank AIDS. The asymptomatic phase may last for years and its presence suggests a persistent conflagration between the virus and the host's immune response. There is considerable evidence that an immune response develops but the response is ultimately inadequate. From the work of others as well as our own, we have constructed a hypothesis which attempts to explain some aspects of the immune response. We propose that HIV-1 preferentially infects a subset of CD4+ lymphocytes which are then either destroyed or altered in their biological functions. Further, we suggest that this subset represents the CD4+ TH1 lymphocyte population. By decreasing the quantity of IL-2 and interferon-gamma produced by TH1 lymphocytes, the production of cytokines by TH2 cells is increased. One of the cytokines produced by TH2 lymphocytes is IL-10, a polypeptide with significant inhibitory properties towards lymphocytes. Sera from patients with frank AIDS have significant lymphocyte inhibitory activities some of which operate through IL-10. Thus, a gradual shift to a TH2-type response and release of increasing amounts of inhibitors eventually prevents the host from replacing destroyed cells or mounting new and appropriate immune responses.
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PMID:Breaking the asymptomatic phase of HIV-1 infection. 791 Jun 37

T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/- 8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell cultures significantly improved recovery of viable cells (71.3 +/- 6.2%, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in this system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [3H]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness.
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PMID:Interleukin-10 inhibits apoptotic cell death in infectious mononucleosis T cells. 804 Feb 67


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