Role of Epstein-Barr virus and interleukin 6 in the development of lymphomas of human origin in SCID mice engrafted with human tonsillar mononuclear cells

Nadal, David; Albini, Boris; Schläpfer, Erika; Bernstein, Joel; Ogra, Pearay L.

doi:10.1099/0022-1317-73-1-113

Cited by 21 publications

(7 citation statements)

References 56 publications

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“…Kinetic studies of the effect of human immunoglobulin preparations on in vitro-induced monokine production indicated a sustained, significant inhibition of IL-6 production in the cultures supplemented with y-globulin (Anderson and Anderson, 1990). In agreement with Nadal et al (1992) we found increased IL-6 levels in 50% of tumorbearing animals. However, IL-6 was not measurable in tumorfree animals, irrespective of y-globulin treatment.…”

Section: Discussionsupporting

confidence: 91%

“…Human IL-6 has been detected in the serum of a majority of tumor-bearing SCID mice reconstituted with human tonsillar mononuclear cells, but not in any animals without human lymphoma (Nadal et al, 1992). IL-6 is a potent B-cellstimulating factor required for the growth of these cells and their terminal differentiation into Ig-secreting plasma cells (Hirano et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

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Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes

Abedi¹,

Christensson²,

Al-Masud³

et al. 1993

Intl Journal of Cancer

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The effect of weekly gamma-globulin injection on the development of human B-cell tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The mice were injected intraperitoneally (i.p.) with human peripheral mononuclear cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors. Animals repopulated with cells from 5 donors received gamma-globulin or saline for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma-globulin-treated groups as compared to the controls. In a separate experiment, the effect of gamma-globulin treatment during the initial 4 weeks after reconstitution was compared to treatment from week 5 to week 8 as well as to a continuous 20-week treatment. The results from this experiment showed that B-cell tumor growth could be prevented just as efficiently when the animals were treated only during the first 4 weeks. In contrast, no preventive effect was seen when the first gamma-globulin dose was given at the beginning of week 5 after reconstitution. Our results indicate that gamma-globulin reduces the frequency of EBV-derived B-cell tumor development and suggest that SCID mice repopulated with human cells represent a useful in vivo model for evaluation of the prophylactic and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative disorders associated with immunosuppression.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes

Abedi¹,

Christensson²,

Al-Masud³

et al. 1993

Intl Journal of Cancer

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“…The production of lymphoma in SC1D mice in our study is consistent with the report that spontaneous lym phomas occur in SCID mice even without any manipula tion [17], The development of B cell lymphoma of human MS cell origin in one of our mice is similar to the one that has been reported in SCID mice injected with human ton sillar mononuclear cells [19]. In that report the donors of human lymphomas were all seropositive for EBV, and EBV genome was detected in the B cell tumors.…”

Section: Discussionsupporting

confidence: 81%

Demyelination following Transfer of Human Lymphocytes into Mice with Severe Combined Immunodeficiency

Lavi

Rostami²

1996

Pathobiology

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Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease in humans. We investigated adoptive transfer of demyelinating lesions into severe combined immunodeficiency (SCID) mice via injection of peripheral blood lymphocytes (PBLs) from MS patients. PBLs from chronic progressive MS patients were injected 2-7 times at monthly intervals into 8-week-old or newborn SCID mice (n = 51). Immunocompetent mice (n = 10) were injected with similar PBLs from MS patients. Other SCID mice (n = 17) were injected with PBLs obtained from healthy human donors. Mice were sacrificed (2-8 weeks after the last injection); brains and spinal cords were studied with HE and myelin stains, and lymphocytic markers. Demyelinating lesions occurred in 2 mice injected with MS lymphocytes and in one mouse injected with cells from a healthy donor. In addition, occasional meningitis, hydrocephalus, periventricular leukomalacia, lymphomas of either mouse or human origin, and splenomegaly occurred in some mice. Thus transfer of PBLs from MS patients or normal controls can occasionally produce inflammatory demyelinating lesions in SCID mice. This phenomenon which does not appear to be specific to MS lymphocytes may be explained by ‘graft-versus-host’ reaction of the human lymphocytes against the mouse tissue.

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“…Furthermore, the level of human IL-6 in mouse serum as produced by transferred human cells was higher in animals which received IL-1 in addition to the implant. The fact that human IL-6 is secreted by engrafted human cells in considerable amounts and can be detected in murine serum has also been described by other authors [29].…”

Section: Discussionmentioning

confidence: 65%

Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local application of human recombinant IL-1β, IL-2 and IL-6

Kühn

Ermann

Sack

1997

Clinical and Experimental Immunology

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The contribution of interleukins produced by most inflammatory cells to chronic arthritis is not well understood. Therefore, we investigated the influence of several human recombinant interleukins (IL‐1β, IL‐2 and IL‐6) on joint swelling, on the inflammatory process, and on serological parameters in a novel animal model of arthritis, the human/murine SCID arthritis. In this model an arthritis is induced by implanting human synovial tissue from patients with rheumatoid arthritis (RA) into the knee joint of mice with SCID. These mice tolerate the xenogeneic implant and develop a mixed human/murine pannus tissue. The interleukins were injected daily for 7 or 14 days after implantation. IL‐1β led to a significant increase in joint swelling. It intensified the inflammatory process accompanied by enhanced migration of murine inflammatory cells into the knee joint. The production of human IL‐6 in the transplanted tissue was stimulated through the application of IL‐1β, and the serum level of human IL‐6 was thus significantly higher than in controls. We could not observe a significant influence of IL‐1β on the production of human IgG or IgM by the implant. The application of human IL‐2 had a weak effect similar to that of IL‐1β, but without statistical significance. Although IL‐6 is a good marker for inflammation in RA, the application of recombined human IL‐6 had no influence on the inflammatory process in this model.

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Role of Epstein-Barr virus and interleukin 6 in the development of lymphomas of human origin in SCID mice engrafted with human tonsillar mononuclear cells

Cited by 21 publications

References 56 publications

Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes

Gamma‐globulin modulates growth of EBV‐derived B‐cell tumors in scid mice reconstituted with human lymphocytes

Demyelination following Transfer of Human Lymphocytes into Mice with Severe Combined Immunodeficiency

Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local application of human recombinant IL-1β, IL-2 and IL-6

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