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Activation-dependent apoptosis in CD4+ T cells during murine AIDS
D A Cohen1, E A Fitzpatrick, S S Barve
1Department of Microbiology and Immunology, University of Kentucky, College of Medicine, Lexington 40536-0084.
Cellular Immunology
|October 15, 1993
Summary
CD4+ T cell apoptosis occurs in a mouse model of AIDS (MAIDS) and HIV infection, but only HIV causes T cell depletion. This suggests cell proliferation balances apoptosis in retroviral immunodeficiencies.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- The depletion of CD4+ T cells in HIV infection is poorly understood.
- Activation-induced apoptosis has been proposed as a mechanism for CD4+ T cell loss.
- The murine retroviral model of AIDS (MAIDS) causes immunodeficiency but not CD4+ T cell depletion.
Purpose of the Study:
- To investigate CD4+ T cell apoptosis in MAIDS.
- To compare CD4+ T cell apoptosis in MAIDS with HIV infection.
- To explore the role of T cell receptor (TcR) signaling in MAIDS-related apoptosis.
Main Methods:
- Analysis of splenic CD4+ T cells from MAIDS-infected and normal mice.
- Induction of apoptosis using anti-CD3 monoclonal antibody (mAb) in vivo and in vitro.
- Assessment of DNA fragmentation and calcium signaling in CD4+ T cells.
Main Results:
- CD4+ T cells from MAIDS-infected mice exhibited apoptotic morphology and DNA fragmentation.
- Anti-CD3 mAb treatment enhanced CD4+ T cell apoptosis in MAIDS-infected mice.
- MAIDS CD4+ T cells showed defective TcR signaling, with diminished calcium response and no proliferation upon stimulation.
- Despite apoptosis, CD4+ T cells were not depleted in MAIDS-infected mice.
Conclusions:
- Activation-induced CD4+ T cell apoptosis is a feature of MAIDS, similar to HIV infection.
- CD4+ T cell depletion is specific to HIV infection and not MAIDS.
- The balance between apoptosis and cell proliferation may dictate CD4+ T cell depletion in retroviral immunodeficiencies.