Cytotoxic cell proteinase gene expression and cytolytic activity by anti-CD3-activated cytotoxic T lymphocytes is sensitive to cyclosporin A but is not dependent on interleukin-2 synthesis.

We have examined the role of interleukin (IL) 2 in the expression of cytotoxic cell proteinases (CCP) 1 and 2, as well as in the induction of major histocompatibility complex (MHC)-unrestricted cytotoxic activity in murine T cell cultures following stimulation with anti-CD3 monoclonal antibody. A dramatic reduction in CCP-1 and CCP-2 gene expression and near absence of cytolytic activity was shown to occur in these cultures when the expression of IL-2 was inhibited by 10(-6) M cyclosporin A (CsA). The inhibitory effect of CsA could not be eliminated by the addition to culture of recombinant IL-2 at concentrations typically present in anti-CD3-stimulated T cell culture supernatants.

Inhibition of DNA synthesis and IL-2 bioactivity in MLR by splenic pregnancy-associated natural suppressor cells involves the production of a TGF-beta 1-like molecule and a second distinct inhibitory factor.

Natural suppressor cells exhibiting a double-negative, immature T cell phenotype have been identified in maternal spleen during syngeneic murine pregnancy. In the present study, splenic pregnancy-associated natural suppressor (SPANS) cells are shown to express alpha/beta T cell receptors. SPANS cell-mediated inhibition of DNA synthesis by spleen cells responding in mixed lymphocyte reactions (MLR) is associated with a reduction in interleukin (IL)-2 bioactivity beginning after 96 h of culture.

Heterogeneity of splenic natural suppressor cells induced in mice by treatment with cyclophosphamide.

Administration of high dose cyclophosphamide (CY, 200 mg/kg body weight) to adult mice induces transient, nonspecific suppressor activity in the spleen of treated animals. Characterization of the CY-induced natural suppressor (NS) cells which inhibit mixed lymphocyte reactions revealed a heterogeneous population of lymphocytes expressing the CD8 T cell marker and the B220 B cell marker, as well as cells bearing the granulocyte-monocyte marker CD11b. On a cell per cell basis the most potent of these suppressors were found to be positive for CD11b.

Soybean agglutinin-positive natural suppressor cells in mouse bone marrow inhibit interleukin 2 production and utilization in mixed lymphocyte reactions.

Although natural suppressor (NS) cells resident in bone marrow (BM) have been the subject of intensive study, the exact nature and mode of action of these potentially important immunoregulatory cells are still uncertain. Here we show that NS cells with potent inhibitory effects on mixed lymphocyte reactions (MLRs) can be isolated from BM of normal adult mice by agglutination with the plant lectin soybean agglutinin (SBA). Complement-dependent lysis of SBA receptor-bearing BM cells with antibodies to asialoGM1, Mac-1, Thy-1.

Reactivity of monoclonal antibody 1E5.B5 with a novel phenotypic marker expressed on a murine natural suppressor cell subset.

Natural suppressor (NS) cells are antigen-nonspecific, MHC-independent immunoregulatory cells that are typically found in murine bone marrow (BM), newborn (NB) mouse spleen, and in splenic tissue of adult mice during pregnancy and following cyclophosphamide (CY) treatment. There has been a pressing need for the development of NS cell-specific monoclonal antibodies (mAb) since NS cells are generally described as null cells which lack the usual phenotypic markers of mature T cells, B cells, and macrophages. Here we present evidence that mAb 1E5.