AEGiS-13IAC: Development of B lymphoma-like lesions in HIV-1 transgenic mice.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Development of B lymphoma-like lesions in HIV-1 transgenic mice.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrB300)

Lunardi-Iskandar Y, Bryant J
Y. Lunardi-Iskandar, Institute of Human Virology, Basic Science, Univ. Md. Biotech Institute, 725 W. Lombard Street Rm N456, Baltimore, Md 21201, United States, Tel.: +1 410 706 09 96, Fax: +1 410 706 00 51, E-mail: lunardi@umbi.umd.edu

BACKGROUND: Non Hodgkin lymphoma `NHL' is one the most common AIDS-malignancies. They are often EBV-negative and the incidence occurs in 3-6% of NHL in HIV-1 infected individuals. The pathogenesis of NHL is not yet completely understood. We have developed a HIV-1 transgenic mouse model with spontaneous B-cell lymphomas.

METHODS: B-lymphocyte colonies `B-CFC' from PBMC's of HIV-1 transgenic mice were collected and expanded in liquid medium using IL-7. Cells were injected subcutaneously in nude mice. All injected nude mice developed tumors within 14 days and metastases in the liver, lungs, spleen, lymph nodes and brain after 30 days.

RESULTS: We analyzed the HIV-1 transgenic mice with B-cell lymphoproliferative disease. We domonstrated that the phenotypes: B220, IgM, IgD, IL-7 receptors, CD40, CD19, CD25, CD43 and CD28, were expressed in peripheral blood and bone marrow. The number of the CD19+ B-cells wre significantly increased. When we analyzed the differents loci of skin tumors, lymph nodes and spleen biopsies it showed abundant CD19+, 28+ cells present in all tissues. In Vitro, culture B-cell colony growth `B-CFC' is very dependent on exogenous IL-7.5x10(6)of b-lymphoma cells were inoculated into the nude mice `>7 days SC post inoculated' and developed b-lymphoma with metastases to the lung, spleen, brain and liver `30 days after post inoculated'. Several cytokines were increased significantly: IL-1, IL-6, IL-8 and the growth factors TNFx, IFNy, bFGF , and HGF'.

CONCLUSION: The b-cell hyperactivation and proliferation in HIV-1 transgenic mice appears to be a direct effect of gp120 in the serum. These findings mimic NHL disease and could be an excellent animal model to study AIDS-associated lymphoproliferative disease and a model to test new treatment strategies.

Keywords: AEGIS, Mice, Transgenic, HIV-1, Lymphoma, Non-Hodgkin, Herpesvirus 4, Human, Interleukin-7, Spleen, B-Lymphocytes, Bone Marrow, Cytokines, Interleukin-6, Lymphoproliferative Disorders, Lymph Nodes, Lymphoma, B-Cell, Interleukin-1, Mice, Animal, In Vitro
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