The role of interleukin-2 as one of the determinants of the balance between immunity and unresponsiveness.
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Animals↗
Biomedical subjects
M Zembala
Publications and source records attributed to M Zembala.
Monocyte subsets in the production of inhibitory factor by Candida albicans-activated human T cells.
Macrophages are essential for the proliferative response of human T lymphocytes to a purified polysaccharide extract from Candida albicans (MPPS). The role of macrophages as antigen-presenting cells in the production of an antigen non-specific inhibitory factor (nsINH) by MPPS-activated T cells was also investigated. Fc receptor positive (FcR+) or negative (FcR-) plastic-adherent mononuclear cells were used as MPPS-presenting cells, and the results show that the FcR- subset is mainly responsible for the release of nsINH from activated T cells.
Antigen-Presenting Cells↗
The role of shed Fc receptor in the regulation of lymphocyte response to phytohaemagglutinin (PHA).
Supernatants from 18-hr cultures of human peripheral blood polymorphonuclear cells (PMN) and adherent cells (AC) inhibited the binding of erythrocyte-antibody complexes (EA) by PMN. The inhibitory activity was lost upon absorption on IgG and Fc, but not on the F(ab')2 fragment of IgG. IgG-binding material (shed Fc receptor--FcR) was reutilized by PMN and AC which had lost their own FcR in vitro. Reutilization was independent of the type of cells from which FcR originated. The FcR-containing material eluted from IgG-coated Sepharose column inhibited PHA-induced lymphoproliferation, probably via prior interaction with monocytes. These results suggest that shed FcR may be freely exchanged between different types of human leucocytes and play a role in the suppression of mitogen-induced T-cell responses.
Cell Adhesion↗
T suppressor factor activity is due to two separate molecules. The Lyt-1(-)2+I-J+ cells of mice primed with antigen make an antigen binding molecule which is only active when complemented by cofactor made by Lyt-1+2(-)I-J+ cells.
Mice primed with picrylsulfonic acid (PSA) and then painted on the skin with picryl chloride produce antigen-specific T suppressor factor (TsF). In contrast unpainted primed mice fail to produce active TsF. This is not due to the absence of the antigen binding part of TsF but to the absence of a cofactor. This cofactor is (a) antigen nonspecific and occurs in potassium chloride extract of normal spleen cells. It also occurs in the 24 hr supernatant of normal cells modified by haptenisation with picryl or the unrelated NP antigen (4-hydroxy-3-nitrophenylacetyl), and in preparations of conventional TsF (PSA/PCl) from painted PSA-primed mice; (b) bears I-J determinants; and (c) is produced by Lyt-1+2(-)I-J+ cells. The antigen binding molecule occurs alone in the supernatant of PSA-primed mice. It lacks I-J determinants and has a molecular weight around 35,000 and 75,000. It is produced by Lyt-1(-)2+I-J+ cells and is only active when complemented by cofactor. However, the complementation is genetically restricted and the restriction maps to the I-J subregion of the MHC.
Animals↗
Nonspecific inhibitor of contact sensitivity made by T-acceptor cells: triggering of T cells armed with antigen-specific T-suppressor factor (TsF) requires both occupancy of the major histocompatibility complex recognition site by soluble I-J product and cross-linking of the antigen recognition sites of the TsF.
The phenomenon of associative recognition, i.e., the recognition of antigen together with major histocompatibility complex products (MHC) was studied in a model system. T-acceptor cells armed with antigen-specific T-suppressor factor (TsF) released a nonspecific inhibitor of the transfer of contact sensitivity when exposed to antigen together with MHC. The MHC product occurred in a KCl extract of cells and behaved genetically and serologically as I-J. Cells armed with anti-picryl or anti-"oxazolone" TsF could be triggered by the corresponding "bis-picryl-L-lysine" and "bis-oxazolone-L-lysine" together with MHC. This suggested that cross-linking of antigen recognition sites on separate molecules of TsF might be required. To investigate this possibility the bifunctional "mixed" hapten "N alpha-picryl-N epsilon-oxazolone-L-lysine," which is univalent with respect to the picryl and oxazolone haptenic groups, was synthesized. This triggered cells armed with a mixture of anti-picryl and anti-oxazolone TsF but not cells armed with either TsF alone. It was concluded that both occupancy of the I-J recognition site and the cross-linking of separate molecules of TsF was required for triggering. Moreover the hapten and the KCl extract could be given sequentially and in either order. This finding suggested that the triggering of the release of nonspecific inhibitor was due to the separate recognition of I-J and antigen and not to new antigenic determinants produced by their interaction.
Animals↗
The use of Fab-Fc recombinant antibodies for studying the mechanism of triggering the effector activities of immunoglobulins.
Immunoglobulin species, recombined from Fab and Fc fragments with anti-red cell specificity were used as cytophilic antibodies in studies of triggering the effector activity of immunoglobulins. Recombinant immunoglobulins containing a single Fab' appeared inactive in binding to cell receptors and triggering antibody dependent cellular cytotoxicity, while those with two Fab' exhibited an activity comparable to intact antibody IgG. The experiments indicate that Fab fragment may interact with Fc and inhibit its binding to cell receptors.
Antibody-Dependent Cell Cytotoxicity↗
Isolation and functional characteristics of FcR+ and FcR- human monocyte subsets.
Human peripheral blood monocytes (M phi) were separated into Fc receptor positive (FcR+) and FcR- subsets by rosetting with O,Rh+ human erythrocytes coated with IgG anti-D antibody, followed by density gradient centrifugation and adherence. The FcR+M phi suppressed PHA- and PPD-induced lympho-proliferation and also exhibited a strong cytostatic effect against tumor cell lines in vitro, but were a poor source of antigen-presenting cells. In contrast, the FcR- subset did not cause suppression but was highly active in the presentation of PPD to T cells and in stimulation of both allogeneic mixed lymphocyte reaction (allo-MLR) and autologous (auto-MLR). PWM-induced immunoglobulin secretion in vitro was greatly enhanced by the FcR- but not the FcR+ subset. Nevertheless, both FcR+ and FcR- subsets showed comparable HLA-DR antigen expression. These results indicate that human M phi, like lymphocytes, may consist of several subsets that differ significantly in their immunologic functions.
Antibodies, Monoclonal↗
Equivalence of conventional anti-picryl T suppressor factor in the contact sensitivity system and monoclonal anti-NP TsF3: their final non-specific effect via the T acceptor cell.
There is considerable confusion over whether the antigen-specific T suppressor factors (TsF) described by different authors are indeed equivalent. This paper investigates whether monoclonal TsF3, obtained from hybridomas derived from mice injected subcutaneously with NP derived spleen cells, is functionally equivalent to the conventional T suppressor factor, produced by mice injected intravenously with chemically reactive, water soluble haptene (picrylsulphonic acid and oxazolone thioglycolic acid). Comparison of monoclonal anti-NP TsF3 with conventional anti-picryl and anti-oxazolone T suppressor factor showed that both armed the non-specific T acceptor cell (Tacc) which was sensitive to cyclophosphamide and adult thymectomy. Moreover, non-specific inhibitor (nsINH) of the transfer of contact sensitivity was released when antigen, together with major histocompatibility complex products (MHC), reacted with conventional or monoclonal TsF on the surface of the non-specific T acceptor cell. The interaction of monoclonal TsF3 with antigen, which led to the release of NsINH, required the presence of MHC and was I-J restricted. However, there was no Igh-1 restriction. The equivalence of conventional anti-picryl and anti-oxazolone TsF has been demonstrated by arming the Tacc with a mixture of these two suppressor factors, and then triggering the release of nsINH with the mixed haptene 'picryl-oxazolone-lysine' which crosslinks separate molecules of TsF. A similar equivalence of conventional anti-oxazolone TsF and monoclonal anti-NP TsF3 was demonstrated using the mixed hapten 'NP-oxazolone-lysine' to trigger the release of nsINH. It was concluded that monoclonal TsF3 and conventional TsF were equivalent, and that both had an indirect mode of action through the non-specific T acceptor cell which led to the production of non-specific inhibitor.
Animals↗
Partial purification and physicochemical properties of human T cell migration inhibitory factor (TIF).
Supernatants from 24 hr cultures of PHA-pulsed human T lymphocytes inhibit the migration of human peripheral blood T lymphocytes and guinea pig macrophages in vitro. The factor responsible for the inhibition of T lymphocytes provisionally called TIF (T cell migration inhibitory factor) was separated from MIF by preparative PAGE, had apparent molecular weight (m.w.) of 1,000-10,000 daltons and isoelectric point of 3.1. TIF activity was resistant to treatment with trypsin, chymotrypsin and neuraminidase but sensitive to PMSF (phenyl-methyl-sulfonyl-fluoride). This suggests that TIF is presumably different from human MIF and may represent a novel lymphokine which preferentially affects T cell migration in vitro.
Animals↗
Output of peritoneal cells into peritoneal dialysate. Cytochemical and functional studies.
The quantitative and qualitative characteristics of cells in the peritoneal dialysate from 12 patients were examined. The number of cells in each subsequent fraction of dialysate decreased, while the differential cell count remained relatively constant for each individual patient. Macrophages, lymphocytes, granulocytes and occasionally mesothelial cells were observed. In 1 patient, plasmocytes were also found. Evident differences in cellularity and cell composition were noticed in dialysate obtained from different patients, especially in 2 patients with bacterial peritonitis there was a rise in cellularity with neutrophilia. Cytochemical (peroxidase, nonspecific esterase activity) and functional (phagocytosis, receptor expression) tests revealed that macrophages form a heterogeneous population of cells.
Adult↗
Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells.
Lyt-1+2+ hapten-specific T suppressor cells (Ts) from mice injected and then painted with picryl or oxazolone derivatives produce hapten-specific T suppressor factors (TsF) in vitro. Stimulation by painting with contact sensitizer (which need not be specific) gives rise to Lyt-1-2+, I-J+, cyclophosphamide-sensitive T acceptor cells (Tacc). When the Tacc population is armed with TsF and then is exposed to specific antigen in the context of I-J-controlled determinants (antigen-presenting, haptenized spleen cells and Ts sharing the same I-J subregion), a nonspecific inhibitor of DNA synthesis (nsINH) appears in the supernatant. This inhibitor suppresses the primary DNA synthetic response to concanavalin A, lipopolysaccharide, and alloantigens in both syngeneic and allogeneic lymphocytes. The nsINH is only effective when added to lymphocyte cultures less than 8 hr after the stimulation with concanavalin A. The nsINH, however, affects neither primary nor secondary cytotoxicity in vitro. These data suggest the mouse immune system is capable of selective regulation of the response to specific antigen by the production of nonspecific soluble suppressor factor(s).
Animals↗
Suppressor cells and survival of patients with advanced gastric cancer.
The association of suppressor cells with survival of patients with gastric cancer was investigated. Phytohemagglutinin (PHA)-induced lymphocyte response and the presence of nonspecific suppressor cells were assessed in patients with different stages of gastric cancer. The presence of suppressor cells was determined by their ability to inhibit the PHA response of normal peripheral blood mononuclear leukocytes. Depression of the PHA response was related to the stage of disease and was also associated with the presence of suppressor cells. Of 245 patients tested, 76 (31%) had suppressor cells. Adherent, nonspecific esterase-positive cells (presumably, monocytes) accounted for the suppression in most cancer patients. The occurrence of suppressor cells and the tumor load were related because the incidence of detectable suppressor cells decreased after surgery in patients with resectable tumor but increased in patients undergoing palliative surgery. In patients with advanced disease who had a generally poor prognosis, the occurrence of suppressor cells was associated with a significantly increased survival. Hence the common view that a depressed lymphocyte response correlates with a poor clinical outcome may not be valid in all types of cancer.
Adult↗
[Massive pulmonary embolism treated surgically under extracorporeal circulation].
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Cholecystectomy↗
Hapten-specific T suppressor factor recognizes both hapten and I-J region products on haptenized spleen cells.
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Animals↗
A follow-up study on chemoimmunotherapy (5-fluorouracil and BCG) in advanced gastric cancer.
Two hundred and seventeen patients with advanced gastric cancer were classified according to the resectability of the tumour into two groups: I, resectable (non-radical surgery), 99 patients, and II, non-resectable carcinoma, 118 patients. Within each group patients were randomly assigned to receive 5-fluorouracil (5-FU) + BCG, 5-FU, or no further treatment (surgery only). BCG was given by scarification. A 2-year follow-up is reported. The group of patients with resectable tumours and receiving chemoimmunotherapy had a statistically significant prolongation of survival compared with the 5-FU and surgery only groups. No differences in survival were observed between these treatment modalities in patients with non-resectable tumour. These observations indicate that chemoimmunotherapy may be of benefit for a selected group of patients with gastric cancer.
BCG Vaccine↗
Cytostatic activity on tumour cells of monocytes from patients with gastrointestinal cancer.
The ability of monocytes from patients with gastrointestinal cancer to inhibit tumour cell growth and suppress PHA-induced lymphocyte response in vitro was assessed. Isolated monocytes, i.e., adherent Fc+ cells from mononuclear cell suspension, were cytostatic but not cytolytic for both K562 line and L1210 lymphoma cells. Monocytes from the patients showed an increased ability to inhibit the growth of L1210 but not K562 line cells. The increased cytostatic activity of monocytes was associated with their suppressor activity. This suggests that suppressor monocytes are also able to arrest tumour cell growth in vitro.
Animals↗
"Activated" monocytes in gastric cancer patients. I. Increased Fc receptor expression, antibody-dependent cellular cytotoxicity and NBT reduction.
The Fc receptor expression, antibody-dependent cellular cytotoxicity (ADCC), and nitro-blue tetrazolium (NBT) reduction of peripheral blood monocytes from 150 patients with different stages of gastric cancer was assessed and compared with results obtained in 77 normal persons and 104 patients with non-malignant diseases of the gut. Monocytes of cancer patients showed an increased ability to form rosettes with human 0, Rh + erythrocytes coated with D-specific antibody. ADCC and NBT reduction were also elevated but no correlation was found with the stage of disease. However, all these phenomena were related to the tumor load as elevated values were the same 4-6 months after surgery in the unresectable-tumor group, while they decreased in patients with resectable tumors. These observations suggest that monocytes of some cancer patients are functionally altered ("activated") in the course of disease.
Adult↗
"Activated" monocytes in gastric cancer patients. II. Suppressor and cytostatic activity in vitro.
The spontaneous nitro-blue tetrazolium (NBT) reduction of monocytes from patients with gastric cancer was assessed and compared with an in vitro monocyte-mediated cytostasis of tumor cell lines and their suppressor activity. The increased NBT reduction correlated with the ability of monocytes to inhibit mitogen-induced normal lymphocyte response and cytostatic activity against L-1210 murine lymphoma cell line. These observations suggest that "activated" monocytes of some cancer patients may play the role of suppressor cells and exert an anti-tumor effect in vitro.
Adult↗