Secretion of γ‐Interferon at the Cellular Level

Andersson, Ulf; Martı́nez-Maza, Otoniel; Andersson, Jan; Britton, Sven; Gaoler, H.; Ley, Marc De; Modrow, Susanne

doi:10.1111/j.1365-3083.1984.tb01021.x

Cited by 23 publications

(13 citation statements)

References 31 publications

(9 reference statements)

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“…Latency III EBV infection has been associated with direct IFN-␤ induction as well as with cytokine-mediated IFN induction (5,55,105). However, IFN-␣1, -␤1, and -␥1 RNAs were not up-regulated in BL41EBV.…”

Section: Vol 76 2002 Ebv Effects On Cell Mrnas 10431mentioning

confidence: 95%

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Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

Carter

Cahir-McFarland

Kieff

2002

J Virol

134

108

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In primary Epstein-Barr virus (EBV) infection, a substantial fraction of peripheral blood B lymphocytes are latently infected and express virus-encoded proteins that are capable of causing continuous B-cell proliferation. The EBV-encoded proteins engender an unusually vigorous and large T-cell immune response which eliminates most of the virus-infected cells. In severely T-cell immune-compromised or otherwise susceptible people, the EBV-infected B lymphocytes can malignantly proliferate (reviewed in reference 90).The EBV gene products that are expressed in primary lymphocyte infection and that stimulate cell proliferation include six nuclear antigen proteins (EBNAs), two latent infection integral membrane proteins (LMPs), two small RNAs (EBERs), and BamA rightward transcripts (BARTs) of uncertain function (reviewed in reference 59). This complex infection, termed latency III, is characteristic of EBV gene expression in EBV-transformed lymphoblastoid cell lines (LCLs) and many lymphoproliferations that occur in immune-deficient humans (23, 95).Many of the EBV effects on cell growth and survival are likely to be mediated by EBV-induced changes in cell gene transcription. Five of the EBNAs can alter cell gene transcription through their direct or indirect interaction with the cellular DNA sequence-specific transcription factors RBP-j/CBF1, PU.1, and AUF1 (35,42,52,53,65,72,91,113,119,123). Furthermore, EBV LMP1 is similar to a constitutively activated CD40 receptor and activates NF-B, Jun/Fos, and AP1 cellular transcription factors (27,28,30,33,36,40,45,50,60,66,81,83). Moreover, EBV LMP2 is similar to a constitutively activated B-cell antigen receptor (BCR) in causing a stable small increase in BCR tyrosine kinase signaling and in desensitizing the cell to BCR-type signal transduction (12, 80). Four of the EBNAs that interact with cellular transcription factors and LMP1 are critical for EBV effects on cell growth and survival, while EBNA3B, LMP2, EBERs, and BARTs are not (19,37,49,56,68,73,76,92,102,108,109).In the experiments reported here, cDNA arrays were used to investigate the effects of EBV latency III infection on cell gene transcription. cDNA arrays are particularly useful in characterizing changes in expression of large numbers of cellular genes (3,4,48,51,57,74,97,100). We compared gene expression in BL41, an EBV-negative Burkitt's lymphoma (BL) cell line, with gene expression in two latency III-expressing cell lines-BL41 infected in vitro with EBV (BL41EBV) and an LCL (IB4) (18,62). In contrast to a comparison of LCLs with resting B lymphocytes, which would identify a large number of cell genes whose expression is up-regulated at various points in the cell cycle, comparison with a non-EBV-infected BL cell line will identify genes that are specifically up-regulated by EBV latency III proteins. However, EBV-regulated genes whose transcription is inherent to the BL phenotype, such as c-myc, may escape detection. MATERIALS AND METHODS Cell

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Section: Vol 76 2002 Ebv Effects On Cell Mrnas 10431mentioning

confidence: 95%

“…Of the genes newly identified as EBV induced, four are known to be interferon (IFN) induced and one, Tyk2, is important in IFN signaling (5,69,112). Since IFNs are not among the arrayed cDNAs, real-time RT-PCR was used to quantify steady-state IFN mRNA levels.…”

Section: Vol 76 2002 Ebv Effects On Cell Mrnas 10429mentioning

confidence: 99%

Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

Carter

Cahir-McFarland

Kieff

2002

J Virol

134

108

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“…In vitro, LCL are potent stimulators of MHC class I-and class 11-restricted EBV-specific T cell responses [9]. The effective interaction of LCL with T cells depends, at least in part, on their blast phenotype, their capacity to process and present soluble antigens [lo], and their constitutive production of lymphokines like IFN [11] and IL1 [12].…”

Section: Introductionmentioning

confidence: 99%

Expression of the Epstein‐Barr virus (EBV)‐encoded membrane antigen (LMP) increases the stimulatory capacity of EBV‐negative B lymphoma lines in allogeneic mixed lymphocyte cultures

et al. 1990

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Epstein-Barr virus (EBV)-negative Burkitt lymphoma (BL) lines are poor stimulators in allogeneic mixed lymphocyte cultures compared to EBV-transformed lymphoblastoid cell lines derived from the same individuals. We have previously shown that the stimulatory capacity of the tumor cells is increased after EBV conversion (Avila-Carino et al., Int. J. Cancer 1987. 40: 691). As a first step towards the identification of the viral gene product responsible for this change we have studied the influence of the EBV latent membrane protein (LMP) on the stimulatory capacity of the EBV-negative BL lines BL41 and DG75 and the B lymphoma line BJAB. Four LMP-transfected sublines of BL41, four DG75 LMP transfectants and one LMP-transfected subline of BJAB showed a significantly stronger stimulatory capacity than the original line. The effect was directly proportional to the amount of LMP detected in each transfectant but was not due to reactivation of LMP-specific memory cells since lymphocytes from EBV-seropositive and -seronegative individuals responded equally. In order to define the relation between LMP expression and induction of stimulatory capacity, DG75 was transfected with constructs containing the LMP gene under the control of an heat-shock promoter. The peak of LMP expression in heat shock-treated cells preceded the appearance of stimulatory capacity by 6-12 h suggesting that critical amounts of the protein may be required to induce the phenotypic change recognized by the T cells. LMP influenced in a dose-dependent manner the expression of the adhesion molecules LFA-1, LFA-3 and ICAM-1 and B cell activation markers CD23 and CD39 in transfected sublines of BL41, but did not affect the expression of these markers in the DG75 and BJAB cell line. All LMP-expressing transfectants showed an increased capacity to form conjugates with unprimed allogeneic lymphocytes.

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“…IFN-g production by EBV-pos individuals resulted from the reactivation of EBV-speci®c memory T cells [9]. The high IFN-g production was likely to be caused by the signi®cantly higher IL-12 release of EBV-pos adults, since IL-12 À secreted by monocytes À strongly induces IFN-g in T and NK cells [23].…”

mentioning

confidence: 99%

The Primary and Memory Immune Response to Epstein–Barr Virus Infection In Vitro is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

et al. 2000

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Jabs WJ, Wagner HJ, Schlenke P, Kirchner H. The Primary and Memory Immune Response to EPSTEIN± BARR Virus Infection In Vitro is Characterized by a Divergent Production of IL-1b/IL-6 and IL-10. Scand J Immunol 2000;52:304±308 Reactivation of latent Epstein±Barr virus (EBV) infection is considered to exert substantial immunomodulating activities. Little is known about EBV's modulating activities on cytokine production upon primary, in contrast to reactivated, infection. Therefore, we investigated the cytokine production of latently infected EBV-positive (EBV-pos) adults upon in vitro EBV stimulation compared to nonimmune age-matched EBVnegative (EBV-neg) donors. Production of interleukin (IL)-1b and IL-6 was strongly decreased in peripheral blood mononuclear cell (PBMC) cultures of EBV-pos adults; in contrast, IL-10 and IL-1 receptor antagonist exhibited signi®cantly higher levels. As expected, interferon (IFN)-g production was almost exclusively observed in EBV-pos donors; it was accompanied by a signi®cantly higher IL-12 synthesis. Experiments employing T cell-depleted PBMC showed similar cytokine levels between EBV-pos and EBV-neg individuals suggesting that reactivation of EBV-speci®c memory T cells was responsible for the divergent cytokine pro®les. Production of viral IL-10 was excluded as a reason for higher IL-10 levels in EBV-pos individuals. In conclusion, our results do not appear to relate to any primary immunological differences between EBV-neg and EBV-pos adults, but show that the EBV-speci®c memory response to latent EBV infection is characterized by some anti-in¯ammatory effects. This might be of relevance upon reactivation of latent EBV infection in vivo and provides further evidence that EBV infection acts in an immunomodulating fashion.

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Secretion of γ‐Interferon at the Cellular Level

Cited by 23 publications

References 31 publications

Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

Epstein-Barr Virus-Induced Changes in B-Lymphocyte Gene Expression

Expression of the Epstein‐Barr virus (EBV)‐encoded membrane antigen (LMP) increases the stimulatory capacity of EBV‐negative B lymphoma lines in allogeneic mixed lymphocyte cultures

The Primary and Memory Immune Response to Epstein–Barr Virus Infection In Vitro is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

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