Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
Essential role for T cells in human B-cell lymphoproliferative disease development in severe combined immunodeficient mice.
Br J Haematol. 2000 Jun;109(3):600-10. Unique Identifier : AIDSLINE MED/20345415 Johannessen I; Asghar M; Crawford DH; Department of Medical Microbiology, The University of Edinburgh; Medical School, UK.
Abstract:
Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease (BLPD)-like lesions develop in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors. We used this model to investigate the pathogenesis of EBV-associated BLPD. Tumour incidence fell from 81% to 11% when only B cells were inoculated, suggesting a key role for T cells in tumour formation. This was further underlined by the reduction in tumour incidence from 76% to 7% when PBMCs were depleted of CD4 positive (+ve) helper T cells. Tumour outgrowth was also reduced when PBMC were depleted of CD8 +ve, CD45RA +ve or CD45RO +ve T cells. The majority of PBMC-derived tumours analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) expressed mRNA for interleukin (IL) 2, 4, 6, 10 and interferon (IFN) gamma. This is the cytokine pattern seen in activated T cells and includes B-cell growth factors. In situ hybridization studies confirmed that the tumour cells themselves express the growth factors, which is consistent with autocrine-stimulated tumour growth. Our results suggest the following sequence of events: (1) T cells are essential for the initial outgrowth of tumorigenic EBV +ve B cells in vivo; (2) the neoplasm sustains its growth in an autocrine, cytokine-stimulated manner; and (3) established tumours become independent of T-cell help.
Keywords: JOURNAL ARTICLE Animal Antigens, CD45/IMMUNOLOGY Autocrine Communication Cytokines/GENETICS/*IMMUNOLOGY CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Epstein-Barr Virus Infections/*IMMUNOLOGY Human In Situ Hybridization Interferon Type II/GENETICS/IMMUNOLOGY Interleukin-10/GENETICS/IMMUNOLOGY Interleukin-2/GENETICS/IMMUNOLOGY Interleukin-4/GENETICS/IMMUNOLOGY Interleukin-6/GENETICS/IMMUNOLOGY Lymphoma, B-Cell/*IMMUNOLOGY/*VIROLOGY Mice Mice, SCID Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger/ANALYSIS Support, Non-U.S. Gov't T-Lymphocytes/*IMMUNOLOGY 001030
A00A1138
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
