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

The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated.
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PMID:Infection of human thymocytes by Epstein-Barr virus. 170 54

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

Activated lymphocytes, as identified by HLA-DR expression, associated with acute Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) were shown to be a heterogeneous population containing significantly elevated cytotoxic/suppressor (CD8) T cells, natural killer (CD16) cells and helper (CD4) T cells. CD8 T cells were the primary activated population representing 24.5% of the total lymphocyte population. The activated CD4 T cells and natural killer cells accounted for 6.7% and 3.5% of the total lymphocyte population, respectively. Analysis of serum soluble interleukin 2 receptors (IL-2R) demonstrated significantly (p less than 0.001) elevated levels in the serum of acute IM patients compared with normal controls. Elevated levels of serum IL-2R were correlated (r = 0.67) with increased percentages of Leu 2a+/HLA-DR+T cells (i.e., activated CD8 T cells). Patients with X-linked lymphoproliferative syndrome and virus-associated hemophagocytic syndrome, two syndromes associated with severe acute EBV infections, demonstrated the most dramatic increase in serum IL-2R levels. These data demonstrate that EBV is associated with intense immune stimulation and that during acute IM activated lymphocytes, other than the CD8 T cells, may contribute to the immune response to EBV.
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PMID:Activated lymphocytes during acute Epstein-Barr virus infection. 311 18

To characterize the abnormalities of natural killer (NK) cells in childhood lymphohistiocytic syndrome (LHS), we investigated the number and cytolytic functions of circulating NK cells in 10 LHS children using flow cytometry, 51Cr-release and single-cell assays. In the active phase, the numbers of CD16+ or CD56+ cells and NK activity were normal in more than half of the patients or otherwise decreased. Despite the treatment with interferon-gamma (IFN-gamma) there was no significant increase in NK activity in the children with LHS: the values (mean +/- S.D.) of 32.2% +/- 14.2% became 35.0% +/- 13.3% (P > 0.05) when the control values changed from 45.5% +/- 8.5% to 54.2% +/- 10.1% after the stimulation. However, the NK cells normally responded to interleukin 2 (IL-2). In contrast, NK cells from 9 patients with infectious mononucleosis (IM) responded well to both IFN-gamma and IL-1 (P < 0.01). At the single-cell level, their NK cells had defective recycling capacity with normal killing capacity. The maximal recycling capacity (MRC) values (mean +/- S.D.) were 3.6 +/- 0.8 as compared to the control value of 5.5 +/- 0.9 (P < 0.01). Two of the patients studied had extremely high levels of serum IFN-gamma (9.8 U/ml and 158.0 U/ml) as compared to the control value of < 0.4 U/ml. NK cells may have been strongly stimulated by IFN-gamma in vivo, which probably yields superficially normal NK cell activity in the face of the absence of responsiveness to IFN-gamma but not to IL-2. The defective recycling may be another abnormality of NK cells in LHS.
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PMID:Absence of responsiveness to interferon-gamma but not to interleukin 2 and depressed recycling as natural killer cell abnormalities in childhood lymphohistiocytic syndrome. 808 21

The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p < 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p < 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl-2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.
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PMID:The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory. 834 Jul 52