Inhibition of sphingolipid synthesis down-modulates CD4 expression by peripheral blood T lymphocytes and T lymphoma cells

Biochemical and Biophysical Research Communications
S L TammaR F Coico

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.

Citations

Nov 6, 2007·Biological & Pharmaceutical Bulletin·Jae Youl Cho
Apr 23, 2009·Virus Research·Abdul A Waheed, Eric O Freed
Aug 27, 2010·Viruses·Abdul A Waheed, Eric O Freed
Sep 21, 2018·Frontiers in Immunology·Jon Ander Nieto-GaraiHans-Georg Kräusslich

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