| Co-Investigator(Kenkyū-buntansha) |
SANO Kunio University of Tokyo, Faculty of Medicine, Research Associate, 医学部(医), 助手 (20192601)
TADA Tomio University of Tokyo, Faculty of Medicine, Professor, 医学部(医), 教授 (10009136)
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| Research Abstract |
The present studies were carded out by utilizing various T cell clones to characterize : (1) The influence of the T cell maturation environment on a repertoire of helper T (Th) cells, T augmenting (Ta) cells, and suppressor T (Ts) cells, which were shown to construct a minimal regulatory circuit to regulate a helper function of class II-restricted Th cells, and (2) the mechanisms of involved in suppressive T cell regulation of MHC-restricted Th cell activation of B cells. The present studies demonstrated the several important points.
(1) A repertoire of keyhole limpet hemocyanin-specific Th cells was influenced predominantly by I-A molecule of the T cell maturation environment, whereas a repertoire of Ta was determined by both I-A and I-E molecules. These repertoires were not influenced by the priming with antigen. A repertoire of Ts cell factor-producing Ts cells was not influenced by the T cell maturation environment, but rather was determined by the I-J haplotype of the antigen-prese
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nting cells (APC) utilized for priming with antigen. In contrast, a repertoire of novel cognate type Ts cells, which inhibit class II-restricted Th cell function in a restriction-restricted manner, was influenced by both I-A and I-E molecules of the T cell maturation environment. These results demonstrate the two distinct mechanisms for generating a T cell repertoire : a selection by class II molecules of the T cell maturation environment before the priming with foreign antigen and a selection by priming with APC and antigen.
(2) The activated CD4^+ Ts cells could inhibit the increase of intracellular Ca2^+ of Th Clones induced by anngen-pulsed APC. The identity of MHC restriction-specificities was required for the instant suppression of Ca2^+ influx of Th clones, while a longer period of activation of Ts clones was needed to suppress the response of Th clones having different MHC restrictions.
(3) A strict selectivity was found in the suppressive activity of Ts clones in that Ts clones could suppress the Ca2^+ responses of Th1 and Th2 clones but not other CD4^+ Ts clones.
(4) Both CD4^+ and CD8^+ Ts clones released soluble immunosuppressive factors upon stimulation with immobiized anti-CD3 antibody. CD8^+ clones could suppress the proliferative response and helper function of Th cells by releasing IL10 and TNFalphabeta, respectively. In contrast, CD4^+ Ts clones suppress only Th cell-mediated antibody formation by the factors different from any known interleukins including _<gamma>FN and TGF_<beta>. Therefore, CD4^+ and CD8^+ Ts clones mediate suppressive effect on immune responses by the different mechaisms. Less
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