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 microg/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(+) TCRalphabeta(+) 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.
Zhou
Hong
H
Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Jiao
Zhijun
Z
Pan
Jijun
J
Hong
Jian
J
Tao
Jiaxian
J
Li
Ningli
N
Zhou
Yun
Y
Zhang
Jingwu
J
Chou
Kuang-Yen
KY
D019380:Anti-HIV Agents / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D016753:Interleukin-10 / Q000378:metabolism* / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015978:Trichosanthin / Q000494:pharmacology*
D019380:Anti-HIV Agents; C508609:IL10 protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D015978:Trichosanthin