T3-Ti receptor triggering of T8+ suppressor T cells leads to unresponsiveness to interleukin-2.
Bensussan A., Acuto O., Hussey RE., Milanese C., Reinherz EL.
T3-associated disulphide linked heterodimers (Tin) comprised of clonally unique alpha-chains of molecular weight (MW) 49,000-54,000 and beta chains of MW 43,000 have been identified as the antigen receptors on human cytotoxic effector and inducer T-lymphocytes. Crosslinking of Ti molecules by either the appropriate nominal antigen/MHC specificity or anti-clonotypic monoclonal antibody results in clonal expansion of such cells via induction of IL-2 receptor expression, endogenous IL-2 release and IL-2-IL-2 receptor interaction. To determine whether analogous antigen receptor molecules and autocrine growth mechanisms are utilized by suppressor T-cells, we produced an anti-clonotypic monoclonal antibody against a non-cytotoxic T8+ suppressor T-cell, T8AC6, which defines a T3-associated disulphide-linked heterodimer of similar molecular weight to the above clonotypes. We find that Te-Ti triggering of suppressor clones (T8AC6, T8AC7 or T8RW) does not result in IL-2 production or T-cell proliferation and in contrast to inducer clones, also leads to a transient IL-2 unresponsive state. We suggest that such T3-Ti receptor mediated autoregulation of suppressor T-cell growth is necessary in the facilitation of initial inducer T-cell activation following antigenic perturbation.