Suppressor T cell (Ts) lines have been generated and maintained in culture for over one year. Cells from these lines suppress proliferation by primed lymph node cells and antibody production by primed spleen cells. Ts were originally obtained from either spleens of mice rendered tolerant to human gamma globulin (HGG) or short-term cultures of normal spleen cells. Ts from these two sources have previously been shown to exhibit antigen specificity in that only HGG-specific immune responses were suppressed. Prolonged culture of Ts, however, leads to 2 events: an enrichment for suppressive activity in the cultures; and a polyclonal activation of Ts which is demonstrated by the acquired ability of Ts cell lines to regulate responses to antigens other than HGG. Ts cell lines still contain HGG-specific Ts which can be isolated by their capacity to bind to HGG-coated plates. Only HGG-specific immune responses are suppressed by the HGG-binding Ts.
No abstract
The induction of T cell tolerance in vitro was investigated by using HGG-specific murine helper T cell (Th) clones and cell lines. It was found that exposure of Th to monomeric HGG (tolerogen) for 18 hr rendered the Th unable to reconstitute the PFC response of HGG-primed B cells. The tolerant state was not a result of Th cell death, as up to 100% of Th could be recovered after exposure to the monomer, and in addition, the recovered cells proliferated in response to IL2. B cells were shown not to be significantly affected by the presence of monomeric HGG in amounts calculated to be carried over from the tolerization cultures into the assay cultures. Consequently, it was concluded that interaction between Th and monomeric HGG induced unresponsiveness at the T cell level. A comparison of the tolerogenic potential of monomeric, soluble, and aggregated HGG revealed that only the monomer could induce tolerance in Th. Monomeric HGG was also shown to induce tolerance in an antigen-specific manner. Th reactive to HGG could be tolerized by monomeric HGG, but not Th reactive to FGG or OVA. Helper function of Th was also shown to be antigen specific in that HGG-reactive Th helped only HGG-primed B cells. Certain HGG-specific Th clones were found to be refractory to tolerization with monomeric HGG, whereas other clones derived from the same uncloned cell line were tolerizable.
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