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How does HIV cause AIDS? The homing theory.
1Departments of Microbiology, Immunology and Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. mcloyd@utmb.ed
Molecular Medicine Today
|February 26, 2000
Summary
HIV infection causes CD4+ T cell depletion by upregulating L-selectin, prompting cells to migrate to lymph nodes. There, homing signals induce apoptosis, explaining the bystander effect and CD4+ T cell loss in HIV patients.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- The precise mechanism of CD4+ T cell depletion in HIV infection is not fully understood.
- Existing theories do not comprehensively explain all observed clinical events in patients.
- HIV binding to resting CD4+ T cells has been shown to upregulate L-selectin.
Purpose of the Study:
- To investigate the role of L-selectin upregulation and homing receptor signaling in HIV-induced CD4+ T cell depletion.
- To propose a mechanism explaining the rapid loss of CD4+ T cells in blood and the bystander effect in lymphoid tissues.
Main Methods:
- Analysis of recent studies on HIV binding to CD4+ T cells and L-selectin expression.
- Hypothesizing the consequences of enhanced homing to lymph nodes.
- Examining the role of secondary signals through homing receptors.
Main Results:
- HIV binding upregulates L-selectin on CD4+ T cells, enhancing their homing to lymph nodes.
- This migration explains the faster depletion of CD4+ T cells in blood compared to lymphoid tissues.
- Homing receptor signals induce apoptosis in these cells within lymph nodes, contributing to the bystander effect.
Conclusions:
- HIV-induced CD4+ T cell depletion may result from enhanced homing to lymph nodes followed by apoptosis.
- This mechanism offers a potential explanation for the bystander effect observed in HIV-infected individuals.
- The proposed model could account for numerous clinical observations in HIV pathogenesis.