Immune suppression via IL-4/IL-10-secreting T cells: A nontoxic property of anti-HIV agent Trichosanthin

The activity of Trichosanthin (Tk) has been attributed to its toxicity since this plant protein was used as an anti-HIV agent. However, in this study strong inhibition of human lymphoproliferation to soluble and allogeneic antigens was induced by Tk at 0.005–0.5 μg/ml without causing cell damages including apoptosis. The suppression was dependent on the presence of monocytes that are able to internalize and process Tk molecules as exogenous antigens. Among 39 Tk-primed T cell lines established, those with strong suppressive activity were CD8+ TCRαβ+ with type 2 cytokine secretion profile. Depletion of CD8 cells from total T cells or blocking expression of HLA-DQ molecules diminished Tk’s inhibitory activity. In addition, healthy subjects with HLA haplotype DRB1*0301-DQA1*0501-DQB1*0201 were susceptible to the hyporeaction induced by Tk or a Tk-derived peptide. This indicates that Tk could induce an HLA-associated immune suppression via activating IL-4/IL-10-secreting T cells, which might belong to CD8 Tc2 subset.