Differential expression of the down-regulatory function of CD8 cells in trichosanthin-induced immunosuppression and its genetic control in humans.
Trichosanthin (Tk), a plant protein isolated from a Chinese medicinal herb, was shown in our previous experiments to suppress mitogenic, antigenic and allogeneic responses of human lymphocytes. Two non-toxic pathways, the CD8-dependent and the CD8-independent, were identified as being involved in inducing the suppression. In this communication, we report that, in a subgroup of healthy subjects, only the CD8-dependent pathway was found to operate. In cell cultures from the other subjects, removal of CD8 cells from the culture did not diminish the suppression, implying that the down-regulatory function of the CD8 cells was not expressed in the presence of Tk. Two types of subject, CD8 mediators (M+) (CD8-dependent pathway operating) and non-mediators (M-) (CD8-independent pathway operating), were thus distinguishable. A 'mediation index' (MI) was calculated as MI (%) = RR of CD8-depleted cell culture--RR of non-CD8-depleted cell culture. Of 68 unrelated subjects tested, 21 (30.9%) could be classified as M+, with a mean 'mediation index' of 13.4 +/- 4.0, while 47 (69.1%) were M-, with a mean MI of -5.6 +/- 4.3 (t = 17.2, P < 0.001). The M+ and M- groups exhibited an essentially non-overlapping bimodal distribution of MI. Among the 40 Caucasoids in the panel, nine of 14M+ subjects were HLA-DR7, DQ2 (chi 2 = 14.652, Pc = 0.00084). The two DR7-DQ3 panel members, however, were M-, suggesting that DQ2 might be associated with M+. Segregation patterns in two families revealed that the M+ phenotype is a Mendelian dominant trait.
Chou
K Y
KY
Shanghai Institute of Immunology, Shanghai Second Medical University, China.
Chan
M
M
Bias
W B
WB
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D010375:Pedigree; D010641:Phenotype; D015978:Trichosanthin / Q000494:pharmacology
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015809:HLA-DR7 Antigen; D015978:Trichosanthin