Susan Solliday Rich

SUPPRESSION OF IMMUNE RESPONSES BY PRODUCTS OF ACTIVATED T CELLS

Publisher Summary This chapter focuses on the characteristics of several selected T-cell factors that suppress immune responses. These factors, although apparently distinct in methods of production, biochemical characteristics, and biological activities, share interesting common properties. In a study described in the chapter, the soluble immune response suppressor (SIRS) was secreted into culture supernates by mouse T cells incubated 6–48 h with mitogenic concentrations of ConA. SIRS-containing supernates, when assayed in a final concentration of 1:40 to 1:100, are not cytotoxic but, if added to cultures at initiation, suppress both IgM and IgG PFC responses to a large extent. The SIRS has little effect when added 24 h after culture initiation, and when added at 48 h or later, it does not significantly alter day 5 PFC responses. Physicochemical studies of SIRS have revealed striking similarities to murine migration inhibitory factor.

[31] A soluble T cell suppressor factor for the mixed leukocyte response (MLR-TsF)

Publisher Summary Exposure to cells bearing disparate major (H-2) or minor histocompatibility alloantigens in vivo activates a population of murine splenic Ts; upon further interaction in vitro with priming alloantigens Ts release MLR-TsF that prohibits alloantigen-induced T cell proliferation in the MLR. MLR-TsF suppressive mechanisms are partially characterized, but appear to derive largely from interference with the process of proliferation; while alloantigen induced differentiative events appear to be unaffected. The chapter further explains production of MLR-TsF. Allogeneic H-2 class I H-2K and H-2D antigens on I-C bearing cells, as well as allogeneic I-J and I-C cell surface determinants are each effective antigens for MLR-TsF production. Distinct subpopulations of MLR-Ts are triggered specifically by these different molecules and can be analyzed individually by challenging primed MLR-Ts with stimulator cells displaying the stimulatory antigen of interest. In addition, the chapter also describes Biological assays of MLR-TsF.

Divalent cations and cytochalasin B-sensitive processes in activation, synthesis, and release of mixed leukocyte reaction suppressor factor

Abstract We have examined the possible rotes of divalent cations and of cytochalasin B-sensitive processes in the production of mixed leukocyte reaction suppressor factor (MLR-TsF). Ca but not Mg was strictly required for MLR-TsF production. A requirement for Mg could be demonstrated only under conditions of Ca depletion, suggesting an intimate linkage in divalent cation requirements. Ca was required for synthesis as well as release of the suppressor factor. Cytochalasin B inhibited MLR-TsF production only when present during the first 4 hr of culture; such inhibition was reversible with incubations of up to 16 hr. This indicated that cytochalasin B inhibited early events of activation, rather than synthesis or release of MLR-TsF. It was found that both Ca and Mg were required either before or during the cytochalasin-sensitive steps in the activation sequence. The relationship of cytochalasin B-sensitive events in early activation to the antigenic stimulus per se was established by limited exposure of suppressor cells to allogeneic stimulators fixed to poly- l -lysine (PLL)-coated plates. Maximal stimulation was observed with a 4-hr exposure, and this antigen-dependent commitment was cytochalasin B sensitive.