Spleen cells from adult mice given total lymphoid irradiation or from newborn mice have similar regulatory effects in the mixed leukocyte reaction. I. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation.

Abstract

We added spleen cells from adult BALB/c mice treated with total lymphoid irradiation (TLI) to the mixed leukocyte reaction (MLR) using a variety of responder and stimulator cells. The spleen cells nonspecifically suppressed the uptake of [3H]-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. We also examined the effect of the spleen cells on the generation of antigen-nonspecific and antigen-specific suppressor cells in the MLR. The experimental results suggest that the spleen cells from TLI-treated mice inhibit the generation of nonspecific suppressor cells, but do not inhibit the generation of antigen-specific suppressor cells. Thus, alloantigenic stimulation of normal responder cells in vitro in the presence of spleen cells from TLI-treated mice generates large numbers of antigen-specific suppressor cells, but few cytolytic cells or nonspecific suppressor cells. Similar nonspecific inhibition of the MLR was observed with neonatal spleen cells. This in vitro system provides a regulatory model for the induction and maintenance of tolerance in vivo, in which adult mice given TLI or neonatal mice accept allogeneic bone marrow transplants without graft-vs.-host disease.

Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells.

“…This GVH suppression appears to be similar to that found in other systems where BM/lymphoreticular cells are rapidly proliferating: in neonatal mice (12), in adult mice or humans given total lymphoid irradiation (13,14), with irradiation and autologous BM transplants in dogs (15), and after 89Sr (16) or cyclophosphamide treatment in mice (17). In these cases, nonspecific suppressors of normal cell proliferation have been found, and these suppressors bear the phenotype of natural suppressor (or null) cells (13-15, 17, 18).…”

Direct Involvement of Macrophages in Destruction of β-Cells Leading to Development of Diabetes in Virus-Infected Mice

“…The mechanism for the effect of CFA on spontaneously developed diabetes in NOD mice is quite different from that of CFA on STZ-induced diabetes. The administration of CFA early in life may enhance extrathymic mechanisms of tolerance induction to self-antigens by extending and/or amplifying the spontaneously elevated natural suppressor activity that characterizes the postnatal period, as proposed by Sadelain et al (41) and in several previous reports (42)(43)(44)(45)(46). Several previous reports have established that adjuvant administration activates natural suppressor cell activity, ascribed either to suppressor macrophages or nonadherent Thy-1~ natural suppressor cells (38)(39)(40).…”

Radiation damage and immune suppression in splenic mononuclear cell populations

“…In addition to cytoreduction of the lymphoid system, ionizing radiation has been demonstrated to cause active suppression through the induction of suppressor cells which non-specifically suppress lymphocyte proliferative responses [1,2]. Such cells have been termed natural suppressor (NS) cells, and were initially characterized in neonatal rodents but have since been reported among cells derived from spleen following total-lymphoid irradiation (TLI) [3,4], cyclophosphamide administration [5], chronic graft-versus-host disease (GVHD) [6], and tumour growth [7]. Lower levels of NS activity have also been observed in normal bone marrow [8].…”