Abstract

In vivo models are essential for understanding the pathogenesis of infectious diseases. The SCID-hu mouse implanted with human fetal liver and thymus allows normal human thymopoiesis to take place for up to one year. HIV infection of SCID-hu mice results in severe depletion of CD4-bearing thymocytes. The investigators propose to use this model to study how administration of cytokines can influence HIV pathogenesis and immune reconstitution in the human thymus. The investigators will determine which cytokines are involved in regulating T-cell development and HIV production. The investigators will also perform experiments to determine if cytokine treatment can augment renewed thymopoiesis from precursor cells following HIV- induced depletion. Additional studies will assess whether cytokine administration can augment certain antiretroviral chemotherapeutic approaches and stem cell immune reconstitution strategies in vivo. These studies will help to comprehend how HIV infection negatively influences immune function, and may eventually lead to novel therapeutic strategies to treat HIV infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055205-03
Application #
2460158
Study Section
Special Emphasis Panel (ZHL1-CSR-Q (M1))
Project Start
1995-09-30
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Uittenbogaart, C H; Boscardin, W J; Anisman-Posner, D J et al. (2000) Effect of cytokines on HIV-induced depletion of thymocytes in vivo. AIDS 14:1317-25
Korin, Y D; Zack, J A (1999) Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes. J Virol 73:6526-32
Jamieson, B D; Zack, J A (1999) Murine models for HIV disease. AIDS 13 Suppl A:S5-11
Amado, R G; Jamieson, B D; Cortado, R et al. (1999) Reconstitution of human thymic implants is limited by human immunodeficiency virus breakthrough during antiretroviral therapy. J Virol 73:6361-9
Kitchen, S G; Zack, J A (1999) Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 in fetal lymphoid organs: implications for pathogenesis in utero. AIDS Res Hum Retroviruses 15:143-8
Kitchen, S G; Korin, Y D; Roth, M D et al. (1998) Costimulation of naive CD8(+) lymphocytes induces CD4 expression and allows human immunodeficiency virus type 1 infection. J Virol 72:9054-60