Molecular events in the T cell-mediated suppression of the immune response.
To understand the mechanism of T cell-mediated suppression, we have established a number of suppressor T cell (Ts) clones of both CD4+ and CD8+ phenotypes that exert a definite suppressive effect on antigen-induced proliferative response of normal and cloned CD4+ helper T cells (Th). When an antigen-activated Ts clone was added to Th clones that were subsequently stimulated with antigen and APC, the increase of intracellular Ca2+ in the latter was greatly inhibited. The suppression was unidirectional where Ts suppressed Th but not vice versa. A Ts clone could not suppress other Ts clones. Exactly the same suppression of Ca2+ response could be induced by the treatment of T cells with an anti-I-J antibody. The anti-I-J suppressed the Ca2+ response of Th clones induced by antigen-pulsed APC and anti-TcR alpha beta antibody, whereas the responses to anti-CD3 and Con A were not inhibited. The difference in the effect of anti-TcR alpha beta and anti-CD3 suggests that the suppression is caused by a functional uncoupling of TcR alpha beta and CD3. The stimulation of Ts clones with anti-CD3, on the other hand, induced a unique suppressor factor that potently inhibits the antigen- and anti-TcR induced proliferation of CD4+ Th clones.
Tada
T
T
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
Hu
F Y
FY
Kishimoto
H
H
Furutani-Seiki
M
M
Asano
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells; D006801:Humans; D007108:Immune Tolerance; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens