CD4 T CELL DEPENDENT B CELL ACTIVATION IN AIDS LYMPHOMAS

艾滋病淋巴瘤中 CD4 T 细胞依赖性 B 细胞激活

• 批准号: 2108355
• 负责人: DONALD E MOSIER
• 金额: $ 24.92万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2108355
• 关键词: AIDS; AIDS related neoplasm /cancer; B lymphocyte; Epstein Barr virus; HIV envelope protein gp120; RNase protection assay; SCID mouse; antibody receptor; cell differentiation; clone cells; enzyme linked immunosorbent assay; genetic strain; helper T lymphocyte; human immunodeficiency virus 1; leukocyte activation /transformation; lymphoma; mixed tissue /cell culture; neoplastic transformation; oncogenes; tumor suppressor genes; virus antigen

One of the frequent consequences of chronic HIV infection is the development of AIDS associated lymphomas. These are uniformly high grade malignancies of B lymphocytes, and they fall into three histological categories: (i) small, noncleaved cell; (ii) large immunoblastic/plasmacytoid cell; and (3), large cell lymphoma. Involvement of Epstein-Barr virus (EBV) is frequently seen in the immunoblastic tumors, while the other tumor categories show frequent c- myc rearrangements and mutations of the p53 tumor suppressor gene. While EBV+ immunoblastic lymphomas have been observed in HIV infection of hu- PBL-SCID mice, the other AIDS-associated lymphomas have not been seen. We propose to study the link between HIV infection and chronic B cell activation, using PBL derived from HIV-infected individuals as well as normal PBL infected in the context of the hu-PBL-SCID model. The specific aims of the project are to determine the response of resting, peripheral blood B cells or tonsillar, germinal center B cells to T cells or T cell clones infected with HIV or expressing HIV gp120 or gp41. CD4 T cell clones will be chosen on the basis of cytokine production to represent either the Th0, Th1, or Th2 subset. Selected combinations of T cell clones and B cells will be introduced into SCID mice to assess the extent of in vivo B cell proliferation, differentiation, and incidence of tumor formation. Peripheral blood B cells, tonsilar B cells, and follicular dendritic cells will be derived from normal donors and PBL from normal and HIV-seropositive donors. EBV seropositive donors who do not give rise to spontaneous tumors will be used. We will also examine expression of B cell genes that might block apoptosis and represent the first step towards malignant transformation under the differing conditions of T cell stimulation outlined in Aim 1. Expression of bcl-2 and the Epstein-Barr virus genes LMP (which transactivates bcl-2 expression), EBNA-2, and ZEBRA will be analyzed by a sensitive RNase protection assay. PBL and germinal center B cells from EBV-positive and EBV-negative donors will be compared. Finally, we will determine the relationship between different HIV-1 strains and specific activation of B cells expressing the VH3 immunoglobulin variable region. Preliminary evidence shows a correlation between the HIV strain used to infect hu- PBL-SCID mice, the rate of CD4 T cell depletion, and the extent of VH3 B cell stimulation. These data suggest that different gp120 molecules may interact differently with the Ig receptor on VH3-expressing B cells, and/or that the extent of CD4 T cell activation following HIV infection differs markedly among different virus strains.

慢性艾滋病毒感染的常见后果之一是

项目成果

Epstein-Barr virus and lymphoproliferative disease.

Epstein-Barr 病毒和淋巴组织增生性疾病。

• DOI: 10.1097/00062752-199901000-00005
• 发表时间: 1999
• 期刊: Current opinion in hematology.
• 作者: Mosier,DE

Hepatitis C (HCV) genotype and viral titer distribution among Argentinean hemophilic patients in the presence or absence of human immunodeficiency virus (HIV) co‐infection

存在或不存在人类免疫缺陷病毒（HIV）合并感染的阿根廷血友病患者中丙型肝炎（HCV）基因型和病毒滴度分布

• 发表时间: 1997
• 期刊: Journal of Medical Virology
• 影响因子: 12.7
• 作者: G. Picchio;M. Nakatsuno;C. Boggiano;Rebecca Sabbe;M. Corti;J. Daruich;R. PÉREZ‐BIANCO;M. Tezanos;Robert Kokka;J. Wilber;D. Mosier
• 通讯作者: D. Mosier