Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice

Abstract

Indirect evidence indicates that herpes simplex virus (HSV)-specific cytotoxic-T-lymphocyte induction is regulated by suppressor cells. To search for such suppressor effects, supernatant fluids from splenocyte cultures from normal and HSV-immune mice cultured either with or without viral stimulation were tested for their ability to inhibit HSV-specific cytotoxic-T-lymphocyte induction. Only the supernatant fluid from the HSV-stimulated, HSV-immune cultures contained a suppressor activity (HSV-SF). HSV-SF was produced by nylon-wool-purified Thy 1+ cells. HSV-SF was detectable after 3 days of culture and would only suppress cytotoxic-T-lymphocyte induction if HSV-SF was added within 24 h of initiation of the test cultures. HSV-SF was neither dialyzable nor heat stable. Molecular sieve chromatography of HSV-SF yielded multiple peaks of suppressor activity. Although most of these peaks exhibited nonspecific suppressor activity, the suppression mediated by the 90,000 to 150,000-molecular-weight fractions was antigen specific and genetically restricted. These results provide direct evidence for the regulation of HSV-cytotoxic-T-lymphocyte induction by a novel suppressor factor.

Mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: cytotoxic T cells

“…(i) Restricted repertoire. The failure to demonstrate Tc induction with VgD52 could have several explanations, including an absence of Tc precursors reactive with gD antigens or an inappropriate stimulation of regulatory cells (helpers and suppressors) postulated to control Tc induction (10,11,13,36). Since the antigen specificity of the Tc precursor reflects that of the effector Tc, we measured the cytotoxic activities of a variety of lymphocyte populations against target cells expressing gD.…”

“…The nonhistocompatible targets were A31 (H-2d) and BALB/c byj LPS blast cells (H-2d), respectively. induce suppressor cells and factors, an experimental design used previously in our laboratory to show HSV-specific suppressor mechanisms was used (11,13). As before, the incubation of HSV-immune splenocytes or DLN cells with HSV resulted in the induction of suppressor factors that inhibited the development of secondary HSV-specific Tc in in vitro induction cultures (Fig.…”

“…ously been shown to produce near optimum amounts of suppressor activity (11). The cultured cells were pelleted by centrifugation (500 x g, 10 min) and kept as a source of suppressor cells.…”

Regulation of herpes simplex virus-specific cell-mediated immunity by a specific suppressor factor

“…The above information regarding the characterization and biological activity of suppressor cascades and suppressor factors has resulted from studies of immune responses to haptens, alloantigens, and other noninfectious antigens. Nevertheless, suppressor mechanisms apparently regulate the immune responses to a variety of infectious agents, including bacteria (10,36,40), fungi (38), protozoans (8,37,46,47), helminths (14,19,44), and viruses (7,9,20,21,23,32,33,35,39,43,45). The role that these suppressor cells have in the disease process remains unclear.…”

“…The role that these suppressor cells have in the disease process remains unclear. For example, both suppressor cells and factors were shown to influence various aspects of immune responsiveness to herpes simplex virus (HSV) (21,23,39,45), but the implication of such suppression in the pathogenesis of herpesvirus infections remains to be established. One attractive proposal was that suppressor cell activity played an important role in recrudescent herpetic disease (23,48,49).…”