The Role of Suppressor Cells in the Production of Macrophage Migration Inhibition Factor

The production of migration inhibition factor (MIF) by human peripheral blood lymphocytes and guinea pig lymph node lymphocytes, in response to mitogen, concanavalin A, or antigen, tuberculin, has been studied. Suppressor cells have been depleted by in vitro ageing of cultures for 24 hours, and this has resulted in a significant increase in MIF activity. Reconstitution of the aged lymphocyte population by the addition of fresh lymphocytes results in a suppression of MIF production. When lymphocytes, which have been cultured for 24 hours in the presence of antigen or mitogen to generate suppressor cells, are added to aged cultures MIF production is inhibited. These results suggest that suppressor cells play a regulatory role in the production of MIF.     

The Role of Suppressor Cells in the Production of Macrophage Migration Inhibition Factor

The production of migration inhibition factor (MIF) by human peripheral blood lymphocytes and guinea pig lymph node lymphocytes, in response to mitogen, concanavalin A, or antigen, tuberculin, has been studied. Suppressor cells have been depleted by in vitro ageing of cultures for 24 hours, and this has resulted in a significant increase in MIF activity. Reconstitution of the aged lymphocyte population by the addition of fresh lymphocytes results in a suppression of MIF production. When lymphocytes, which have been cultured for 24 hours in the presence of antigen or mitogen to generate suppressor cells, are added to aged cultures MIF production is inhibited. These results suggest that suppressor cells play a regulatory role in the production of MIF.     

Mechanism of Action of Suppressor Cells

The addition of a small proportion (10%) of in vivo concanavalin-A (Con-A)-activated spleen cells to normal spleen cell cultures suppressed the primary immune response to sheep erythrocytes (SRBC) but had no effect on the thymus-independent primary immune response to 3,5-dinitro-4-hydroxy-phenacetyl-conjugated lipopolysaccharide. When Con-A-activated cells were added after 24 h, there was no suppression of the anti-SRBC response but rather an enhanced response when few cells were admixed. Con-A-activated cells did not influence activation of normal cells by polyclonal T- and B-cell activators. It is concluded that Con-A-induced suppressor cells do not act on B cells but rather on helper cells (T cells or macrophages) at a very early stage of the immune response to thymus-dependent antigens.     

Functional Characterization of Hapten-Specific Suppressor Cells

T cells from animals suppressed against a given hapten, trinitrophenyl (TNP), were analysed for their capacity to inhibit the humoral B-cell response against the hapten and/or a complex antigen, horse erythrocytes (HRBC), coupled or not to the hapten. As expected, suppression of the response to HRBC in all experiments required coupling to TNP. However, the suppressing capacity of the T cells varied with the stage of the B cells, with no detectable suppression occurring if already primed carrier-specific B cells were used. Hapten-specific T helper cells could, however, be induced in hapten-suppressed mice, when hapten-carrier conjugates were used as immunogen. Under these conditions normal efficiency of induction of carrier-specific T helper cells was observed, and this probably also applied to hapten-specific T helper cells to the same extent. This assumption was strengthened by using the hapten-binding capacity of the suppressor T cells and Lyt-1/2-specific sera to subdivide physically helper and suppressor function.     

Effects of Methylprednisolone on the in Vitro Induction and Function of Suppressor Cells in Man

The effects of the steroid methylprednisolone on the induction of suppressor lymphocytes in human mixed lymphocyte cultures (MLC) have been examined. Concentrations of methylprednisolone (MP) sufficient to inhibit both the cellular proliferation and the generation of cytotoxic lymphocytes in MLC appeared to enhance the induction of suppressor cells in these cultures. Maximum enhancement of suppressor cell induction occurred at an MP concentration of approximately 1 microgram/ml. Moreover, the presence of low concentrations of methylprednisolone, not sufficient to inhibit proliferation in MLC, significantly potentiated the inhibiting effect of suppressor cells on cellular proliferation. The inhibition observed by the combined effect of MP and suppressor cells was equivalent to that seen using five times as many suppressor cells alone.     

Stromal Cells Attract B-Cell Progenitors to Promote B-Cell–B-Cell Contact and Maturation

The in vitro differentiation of B-lineage progenitors into Ig-secreting mature B cells has classically required a co-culture system containing lipopolysaccharide (LPS) and stromal cells. We have previously showed that B-lineage progenitors cultured in round-bottomed wells can mature and secrete immunoglobulin M (IgM) on par with cultures containing stromal cells. This clearly demonstrates that any factors essential for progenitor cell maturation can be found in cultures containing media, serum, LPS and B-cell progenitors. However, stromal cells are important for the maturation observed when cells are cultured in flat-bottomed wells. We hypothesized that stromal cells may attract B-cell progenitors and promote contacts between responsive cells, a phenomenon that is mimicked by the cultures in round-bottomed wells. In this study, we explore how stromal cells accomplish these functions. We show that stromal cells attract B-cell progenitors in a pertussis toxin-sensitive manner. The stromal cell line S17 produces the chemokine CXCL12, which is able to induce the chemotaxis of B-lineage progenitors. Chemotaxis can be blocked by a small peptide inhibitor (T134) of CXCR4, the CXCL12 receptor. Further, disrupting chemotaxis can reduce the supportive role played by S17 when B-lineage progenitors are cultured in flat-bottomed wells.     

Negative Regulation of Myeloid-derived Suppressor Cells in Cancer

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with suppressive function on immune response. In this review, we discuss recent studies about mechanisms of expansion and suppressive function of MDSCs during inflammation, infection and autoimmune diseases, as well as pro-angiogenic and pro-metastatic functions of these cells in tumor development. Further, we focus on novel studies of MDSCs and therapeutic approaches to eliminate these cells in cancer.     

Induction of Suppressor Activity on B-Cell Differentiation in Human T-Cell Subset without Fc(IgG) Receptors by Levamisole Administration

A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor-bearing T cells (T gamma cells) increased for 5 days after levamisole intake, but total E rosette-forming cells showed no significant alterations. The generation of immunoglobulin-producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)-stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T-cell activity on B-cell differentiation, which was induced by levamisole intake, was evaluated by co-culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose-dependent suppression on B-cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T-cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in T gamma cells.     

Effects of Hydroxyurea on Concanavalin-A-Induced T-Cell Proliferation

The effects of eliminating cycling precursors by in vivo administration of high doses of hydroxyurea (HU) in populations of mouse spleen T lymphocytes were studied by membrane immunofluorescence identifying mature Thy 1⁺, Lyt 2⁻ and Lyt 2⁺ cell populations and mitogen-induced T-cell growth factor (TCGF) production or reactivity to TCGF. HU treatment results in a sharp decrease in the total number of T cells in mouse spleen, indicating that about 50% of peripheral splenic T lymphocytes have a short survival time in vivo. This depletion is more marked for Lyt 2⁺ cells than for Lyt 2⁻ cells. The decay of TCGF-reactive spleen cells after drug adminstration is similar to that of the overall spleen T-cell population. Conversely, production of TCGF induced by concanavalin A is predominantly affected by HU treatment, indicating a shorter life span of the cell(s) involved in TCGF production.     

Local Active Suppression by Suppressor Cells in the Decidua: A Review

ABSTRACT: The immunological survival of the antigen-bearing mammalian feto-placental unit is determined by the functional properties of the tissues at the feto-maternal interface. Antigen-specific systemic suppressor mechanisms such as suppressor T cells and non-antigen-specific suppressive serum factors appear not to play a major role in protection of the fetus. A novel type of non-MHC specific suppressor cell accumulates locally in the decidua of successfully allopregnant mice. This decidua-associated suppressor is a small lymphocytic cell possessing cytoplasmic granules, lacks T cell markers, and is deficient in number and activity at the implantation sites of viable xenogeneic Mus caroli embryos gestating in the uterus of Mus musculus animals at the time that maternal lymphoid cells begin to infiltrate the xenoembryos. These Mus caroli embryos subsequently resorb. Further experimental studies suggest that the trophoblast cells associated with successful pregnancy recruit bone-marrow derived maternal non-T suppressor cells to the decidua and thus, by an indirect mechanism, may act to protect the fetus from effector cells of the mother's immune system.