Epigallocatechin Gallate Inhibits HIV-1-gp120-Induced Immune Dysregulation and Apoptosis in Human Lymphocytes

Abstract

913 Epigallocatechin Gallate Inhibits HIV-1-gp120-Induced Immune Dysregulation and Apoptosis in Human Lymphocytes C. L. Nance, S. P. Westerfield, V. C. Willis, W. T. Shearer; Texas Children’s Hospital, Houston, TX, Baylor College of Medicine, Houston, TX. BACKGROUND: HIV-1 infection results in impaired immune function by initial binding of the HIV-1 virion envelope glycoprotein, gp120, to the CD4 receptor. This binding induces immune activation/proliferation, cytokine dysregulation, and programmed cell death. Previously, we presented evidence that the green tea catechin, epigallocatechin gallate (EGCG), binds with high affinity (Kd510nM) to the CD4 D1 domain at the gp120 attachment site (Phe43, Arg59, Trp62). We, hereby, present evidence that physiologically relevant levels of EGCG (200-2000nM) prevent these HIV-1-gp120-induced responses in human lymphocytes. METHODS: Human peripheral blood mononuclear cells and CD41 T cells were isolated from HIV-1 seronegative donors. Proliferation was measured by XTT assay. Apoptosis was assessed by flow cytometric analysis of Annexin V binding and Apo-1/Fas (CD95) surface expression. IL10 cytokine production was measured by ELISA. RESULTS: HIV-1-gp120-induced proliferative responses were reversed 46% by EGCG at 2000nM (p<0.01). HIV-1-gp120-induced apoptosis measured by Annexin V binding was reversed by EGCG at 200-2000nM (37%, 47%, respectively) (p<0.01). CD95 receptor expression upregulated by HIV-1-gp120 (100ng/ml) was reversed 32% and 52% with EGCG at 200-2000nM, respectively (p<0.01). HIV-1-gp120-induced IL10 cytokine production was down-regulated 55% with EGCG at 2000nM (p<0.001). The specificity of the EGCG effects was demonstrated by substitution with control catechin, (-)-catechin. CONCLUSION: By binding to the CD4 molecule, EGCG, at physiologically relevant concentrations, counteracts the effects of HIV-1-gp120 on human lymphocytes. This may lead to the restoration of T cell immunity, a goal of immune based therapy in HIV. Thus, EGCG has potential as adjunctive therapy in HIV-1 infection. Funding: NIH