The nature of the atypical lymphocyte in infectious mononucleosis

Giuliano, Vincent J.; Jasin, Hugo E.; Ziff, Morris

doi:10.1016/0090-1229(74)90026-9

Cited by 28 publications

(5 citation statements)

References 20 publications

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“…Infectious mononucleosis (IM) 1 is a usually benign lymphoproliferative disease caused by Epstein-Barr virus (EBV) (1). Atypical lymphocytosis, the major hematologic abnormality of the disease, is due largely but not exclusively to the proliferation of immunologically activated T lymphocytes which are presumably reactive against EBV-infected lymphocytes (2,3). Since EBV transforms resting human B lymphocytes in vitro into continuously dividing cells (4,5), the effects of the virus on cells in vivo have major importance, especially in view of the association of EBV with Burkitt lymphoma, nasopharyngeal carcinoma (6), and immunoblastic lymphoma (7).…”

mentioning

confidence: 99%

Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis.

Robinson¹,

Smith²,

Niederman³

1981

The Journal of Experimental Medicine

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During the acute phase (1 wk of symptoms or less) of infectious mononucleosis (IM), 70--80% of circulating Epstein-Barr virus nuclear antigen (EBNA)-positive cells have differentiated toward plasma cells. Thus the characteristics of the infected cells in the majority of IM patients during early disease are indistinguishable from EBNA-positive tumor cells of a previously reported child who developed lymphoma during IM. IgA and IgG were the most frequent and IgM the least frequent immunoglobulin isotypes detected in EBNA-positive cells. In acute disease EBNA was present in 5.5--20% of T cell-depleted blood lymphocytes but in the 2nd or 3rd wk of illness the number of EBNA-positive cells sharply decreased to 0.4--1.4%. At the same time the fraction of antigen-positive cells containing cytoplasmic immunoglobulins also diminished, suggesting either that differentiation of infected cells was altered during the disease or that nondifferentiated antigen-positive cells had a survival advantage. Both the high proportion of plasmacytic EBNA-positive cells seen during acute disease and the apparent loss of differentiation by these cells later in disease may be regulated by host immunologic factors. Immunoglobulin-producing EBNA-positive cells may be the source of heterophile antibodies and other seemingly inappropriate antibodies usually found in serum during IM; however, increased numbers of noninfected plasma cells were present in some patients and may also be a potential source of these unusual antibodies.

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mentioning

confidence: 99%

Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis.

Robinson¹,

Smith²,

Niederman³

1981

The Journal of Experimental Medicine

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“…In addition to the induction of circulating antibodies from B-lymphocytes [ 25 ], EBV is known to stimulate the activity of T-lymphocytes, facilitating their production of pro-inflammatory cytokines, such as interleukin-2 and interferon-g [ 26 ]. Therefore, the symptoms caused by the virus are primarily considered to be immune-mediated rather than induced directly by cellular toxicity [ 27 , 28 ]. In this context, infection with EBV is often associated with the subsequent onset of immune-mediated systemic disorders, such as systemic lupus erythematosus (SLE) and multiple sclerosis [ 6 , 7 ], or lymphoproliferative disorders, such as Hodgkin’s lymphoma [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions

2016

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Case seriesPatient: Female, 24 • Male, 35Final Diagnosis: EBV-induced infectious mononucleosisSymptoms: Fever • general malaise • lymphadenopathyMedication: —Clinical Procedure: Physical examination and serological testingSpecialty: Infectious diseasesObjective:Rare co-existance of disease or pathologyBackground:Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus (EBV) infection. In adults, the symptoms can often be severe and prolonged, sometimes causing serious complications. Analgesic or antipyretic drugs are normally used to relieve the symptoms. However, there is no causal treatment for the disease.Case Report:Two cases of adult patients with atopic predispositions developed nocturnal fever, general fatigue, pharyngitis and lymphadenopathy after an exacerbation of atopic symptoms or those of allergic rhinitis. Due to the positive results for EBV viral-capsid antigen (VCA) IgM and negative results for EBV nuclear antigen (EBNA) IgG, diagnoses of infectious mononucleosis induced by EBV were made in both cases. Although oral antibiotics or acetaminophen alone did not improve the deteriorating symptoms, including fever, headache and general fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs), such as tiaramide or loxoprofen, completely improved the symptoms quickly after the initiation.Conclusions:In these cases, given the atopic predispositions of the patients, an enhanced immunological response was likely to be mainly responsible for the pathogenesis of the symptoms. In such cases, NSAIDs, that are known to reduce the activity of EBV, may dramatically improve the deteriorating symptoms quickly after the initiation. In the present cases, the immunosuppressive property of these drugs was considered to suppress the activity of lymphocytes and thus provide the rapid and persistent remission of the disease.

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“…The marked T cell-dependence of regression already apparent from earlier work requires that results of this type obtained with UM cell cultures be interpreted with care, since a low incidence of regression could merely be the result of an unusually low proportion of T cells in the initial UM cell population. Such an objection is especially relevant to the present study since the atypical lymphoblasts present in acute IM blood are now known to include cells of B-as well as of T-cell origin (Enberg et al, 1974;Giuliano et al, 1974) with the overall contribution of B cells being higher in the very early stages of the disease (Mangi et al, 1974). However, the results of present experiments using reconstituted TDand T-cell mixtures emphasize that the virtual absence of regression in acute IM patients' cultures is a real phenomenon and not simply due to inadequate numbers of T cells.…”

Section: Discussionmentioning

confidence: 99%

Long‐term T‐cell‐mediated immunity to epstein‐barr virus in man. IV. Development of T‐cell memory in convalescent infectious mononucleosis patients

Rlckinson

Moss

Pope

et al. 1980

Intl Journal of Cancer

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Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response to T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB-virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 X 10(5)/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within 1 week of onset, a much higher mean lymphocyte concentration (3.7 X 10(6)/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 X 10(6)/ml). Six additional were tested 23--83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 X 10(5)/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T-cell-depleted and T-cell-enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB-virus-specific memory T-cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5--23 weeks after onset, and reaches a maximum after about 6 months.

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The nature of the atypical lymphocyte in infectious mononucleosis

Cited by 28 publications

References 20 publications

Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis.

Plasmacytic differentiation of circulating Epstein-Barr virus-infected B lymphocytes during acute infectious mononucleosis.

Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions

Long‐term T‐cell‐mediated immunity to epstein‐barr virus in man. IV. Development of T‐cell memory in convalescent infectious mononucleosis patients

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