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Inhibition of sphingolipid synthesis down-modulates CD4 expression by peripheral blood T lymphocytes and T lymphoma
S L Tamma1, S K Sundaram, M Lev
1Department of Microbiology & Immunology, City University of New York Medical School, 10031, USA.
Abstract:
Recent studies have demonstrated that L-cycloserine, an inhibitor of sphingolipid biosynthesis, interferes with the life cycle of HIV. Experiments with human T cells and CD4+ T lymphoma cells were performed to examine possible mechanisms. L-CS selectively down-modulated CD4 expression without affecting the expression of CD3 and CD8. L-cycloserine also inhibited T cell mitogen responses without affecting IL-2 production. Membranes prepared from L-CS-treated T lymphoma cells showed changes in lipid composition that correlated with changes in membrane microviscosity. These results suggest that normal expression of CD4 may depend upon sphingolipid biosynthesis in contrast with the other CD determinants measured. Selective inhibition of CD4 by L-cycloserine together with its antiviral effects may offer a novel approach for interfering with HIV cell binding and infectivity.
Insights
L-cycloserine, an inhibitor of sphingolipid biosynthesis, selectively reduces CD4 expression on T cells, potentially blocking HIV infection. This suggests a novel therapeutic strategy targeting HIV cell binding and infectivity.
Area of Science:
- Immunology
- Virology
- Biochemistry
Background:
- Sphingolipids are crucial cellular components.
- Human Immunodeficiency Virus (HIV) infects CD4+ T cells.
- L-cycloserine inhibits sphingolipid biosynthesis.
Purpose of the Study:
- To investigate the mechanism by which L-cycloserine interferes with HIV life cycle.
- To examine the effect of L-cycloserine on CD4 expression in T cells.
Main Methods:
- Experiments were conducted using human T cells and CD4+ T lymphoma cells.
- CD4, CD3, and CD8 expression levels were measured.
- T cell mitogen responses and IL-2 production were assessed.
- Membrane lipid composition and microviscosity were analyzed.
Main Results:
- L-cycloserine selectively down-modulated CD4 expression.
- CD3 and CD8 expression remained unaffected.
- T cell mitogen responses were inhibited, but IL-2 production was not.
- Changes in membrane lipid composition correlated with altered microviscosity.
Conclusions:
- Normal CD4 expression appears dependent on sphingolipid biosynthesis.
- L-cycloserine's selective inhibition of CD4 and antiviral effects present a novel approach against HIV.
- This strategy may interfere with HIV cell binding and infectivity.