[Modulation of T-cell-mediated immune responses by trichosanthin via antigen processing and presentation].
It has been shown in our previous study that the lymphoproliferation to allo- or soluble antigens could be inhibited when T cells were cocultured with antigen presenting cells (APCs) pulsed with Trichosanthin (Tk), a plant protein purified from a Chinese medicinal herb Trichosanthes kirilowii Maximovich. In this paper, data are presented dealing with the mechanism by which the Tk functioned as a down modulator. APCs of human peripheral blood were first treated with one of inhibitors of antigen processing (chloroquine, leupeptin or cycloheximide), followed by pulsed with Tk, and then added into a T cell culture with stimulators PMA and A 23187. The suppression of lymphoproliferation was observed to be obviously diminished or totally disappeared. In contrast, when CyA was used to replace the Tk for pulse-treatment of APCs that had received the same pretreatment with the inhibitors, no significant change was detected for the suppression, suggesting that the Tk might use a different pathway to induce hyporeactivity and that the pathway was concerned in APC's function of antigen presentation. This view obtained support from our immuno-histochemical examination of the Tk-pulsed APCs. By preparing colloidal gold-labelled Tk (Tk-G particle), we were able to show that the Tk-G, when incubated with APCs and T cells at 37 degrees C for two hours and washed, was visualized under the electronic microscope to be bound to APCs', instead of T cells', membrane surface and internalized cells' into endosomes. And then the Tk-G particles were further identified within lysosomes. In this way, the Tk molecules were subjected to be processed as an external antigen and might be presented to T cells to activate certain T subsets that in turn mediated the immunosuppression. This course was capable of, as expected, being interrupted by antigen processing inhibitor, especially by chloroquine.
Li
N L
NL
Shanghai Institute of Immunology, Shanghai Second Medical University.
Zheng
Z X
ZX
Shen
B H
BH
Chou
G Y
GY
D017951:Antigen Presentation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D015978:Trichosanthin / Q000037:antagonists & inhibitors*
D007976:Leupeptins; D015978:Trichosanthin; D002738:Chloroquine; C032854:leupeptin