AEGiS-07IAC: Mechanisms of ganglioside-induced modulation of CD4 molecule

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Mechanisms of ganglioside-induced modulation of CD4 molecule

Int Conf AIDS 1991 Jun 16-21; 7:102 (abstract no. M.A.1043)
Saggioro D, Panozzo M, Calabro ML, Callegaro L, Chieco-Bianchi L; University of Padova, Italy

OBJECTIVE: To study the mechanism of monoganglioside GM1 induced CD4 down regulation in CD4 positive cells.

METHODS: 1) CD4 down-modulation was measured by flow cytometric analysis in T cell lines and in HeLa cells expressing a CD4 molecule defective for the cytoplasmic region; 2) HIV-infection in GM1-treated cells was evaluated by RT analysis and by CAT assay; 3) Northern blot analysis of specific CD4 mRNA expression in presence of GM1.

RESULTS: The complete down-modulation of CD4 antigen requires one hour of GM1 treatment (250 ug/ml) and is promptly reversed when the monoganglioside is removed. However, the comparative analysis of exogenous GM1 loss with CD4 re-expression indicates that exogenous GM1 loss from cell membrane is slower than CD4 re-expression. GM1 cells treatment is always accompanied by an inhibition of HIV infection. Contrary to TPA-induced CD4 down-modulation, synthesis of CD4-specific mRNA is not affected by ganglioside treatment. Furthermore, GM1 induces down-modulation of CD4 molecules defective for the cytoplasmic region while TPA treatment has no effect in cyt- CD4 HeLa cells.

CONCLUSION: GM1-induction of CD4 down-modulation may act through mechanisms which do not require the phosphorylation of CD4 cytoplasmic domain.

Keywords: AEGIS, Antigens, CD4, Gangliosides, T-Lymphocytes, Down-Regulation, HIV Infections, Hela Cells, Cell Line, Human, Cats, Animal, genetics, ICA7
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MA1043