Abstract

Patients with AIDS are at increased risk of developing non-Hodgkin's lymphomas. Speculation exists that (a) abrogation of normal immune surveillance, (b) virus-stimulated production of growth cytokines or factors, (c) protracted stimulation of immunocytes through chronic exposure to viral antigens, or (d) intercellular activation or modulation of other viruses infecting """"""""bystander"""""""" cells may function alone or in concert to increase the risk of malignant lymphoma in patients with AIDS. To determine the potential mechanism(s) responsible for HIV-associated lymphomas, the investigators will perform a molecular micro-dissection of hyperplastic or dysplastic lymphoid tissue specimens from patients with AIDS. These studies will allow them to examine the antibody genes expressed by clonally related B cells for evidence of somatic diversification typical of a secondary immune response, for the presence and distribution of potentially oncogenic opportunistic virus (e.g. Epstein-Barr virus, EBV), and for HIV-encoded and HIV-induced factors or cytokines that may modulate the host response to or the pathogenesis of EBV. In order to evaluate the relevancy of a mouse model system to the study of AIDS-associated B cell lymphomagenesis, parallel studies will be performed on the spontaneous lymphomas that occur in mice with SCID six to twelve weeks after intraperitoneal injections of peripheral blood mononuclear cells (PBMC) from healthy individuals. In addition, the frequency, kinetics and character of lymphomagenesis in such mice receiving PBMC with and without lethally irradiated cell lines expressing genes derived from or activated by HIV will be evaluated. Finally, the investigators will examine other effects (both direct and indirect) that HIV tat, TGF-beta and/or other HIV-induced cytokines have in modulating the biology of Epstein-Barr virus infection of human B lymphocytes in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054755-04
Application #
2096130
Study Section
Special Emphasis Panel (SRC (52))
Project Start
1991-03-14
Project End
1995-02-28
Budget Start
1994-03-01
Budget End
1995-02-28
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093