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Biomedical subjects

W Uracz

Publications and source records attributed to W Uracz.

At least 37 records · Page 2Linked to original sources
PubMed1988

Iat epitopes on T cell receptor for self MHC class II determinants.

Anti-Iatk monoclonal antibodies (mAbs) were found to inhibit syngeneic mixed lymphocyte reaction (SMLR) of mice with k and a haplotypes (H-2k and H-2a) of the major histocompatibility complex (MHC) by acting on responder T cells but not stimulator cells. Only the early phase of SMLR was inhibited by anti-Iat mAbs. The inhibitory effect was due to the blocking of autoreactive T cells but not induction of suppressor lymphocytes. Cross-linking of Iat epitopes induced T cell proliferation of k haplotype strain. The inhibitory pattern of SMLR by four anti-Iat mAbs varied among different strains of mice. The inhibitory pattern seemed to depend on MHC and unidentified non-MHC background genes possessed by stimulator cells, suggesting that the shape of the MHC recognition site must have different conformation depending on both MHC and non-MHC gene products recognized. However, the inhibitory pattern of SMLR by anti-Iat mAbs of strains which differ at the I-J locus: B10.A(5R) and B10.A(3R) was dependent on the genotype of stimulator cells. The same was observed in B10.S(9R) and B10.HTT strains. The inhibitory activity of anti-Iat mAbs was entirely directed against responder T cells and was not passively carried out by the stimulators. It was concluded that Iat epitopes are I region controlled determinants that are utilized by T cells as receptors for self Ia antigens. It is suggested that anti-Iat mAbs react with an idiotype on the receptor(s) for Ia or I-J, or possibly a "receptor" for these receptors.

Animals↗
PubMed1987

Immunologic defects as possible causes of therapeutic failures in children with transposition of the great arteries.

Recurrent and severe infections and absence of thymic shadow in X-ray examination were observed in children with the transposition of the great arteries (TGA). Among 45 children (29 boys and 16 girls) with TGA whose age ranged from 3 days to 16 years and who were hospitalized during 1 year, infectious diarrhea was observed in 77.7% cases, urinary tract infections in 44.5%, respiratory tract infections in 42.2%, sepsis in 17.5%, and meningitis in 8.8%. Nine of the children died, sepsis was a cause of death in seven children, and there were postsurgical complications in two children. Immunologic abnormalities in children with TGA included a decreased level of T-lymphocytes and T29 degrees subpopulation, impaired mitogen-induced lymphoproliferation in vitro, and increased nitro blue tetrazolium (NBT) reduction activity of monocytes. Impaired parameters of cellular immunity correlated with worst clinical status. No disorders of humoral immunity were observed. These observations may be important for forming opinion about proper therapy and the cause of death in children with TGA.

Bacterial Infections↗
PubMed1986

Serial immunological testing in patients with gastric cancer.

Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations Ta and T29o was unchanged except depression of T29o in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU + BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.

Adult↗
PubMed1986

Regulation of human lymphocyte response in vitro by monocytes and their subsets.

This paper summarizes the observations on functional heterogeneity of human peripheral blood monocytes (MO). MO are required as accessory cells in lymphoproliferative responses in vitro, but they also inhibit such responses when added in large numbers. Most of human MO express Fc receptors (FcR), but a minority of MO do not possess these receptors as assessed by functional assays. Isolated FcR+ and FcR- MO subsets differ in their functional properties. The FcR+ MO are mostly responsible for the suppression of lymphoproliferation and cytostatic activity against tumour targets, while FcR- MO possess strong antigen-presenting capacity and also the ability to stimulate auto- and allo-MLR. The FcR- MO subset is enriched in cells expressing HLA-DQ determinants, and their ability to present antigen is blocked by anti-DQ but not by anti-DR monoclonal antibodies. In long-term cultures the FcR+ but not FcR- MO induce suppressor T cells which then inhibit antigen-driven lymphoproliferation. PWM-induced Ig synthesis in vitro is enhanced when FcR- MO are added at the beginning of culture. In contrast, FcR+ MO suppress this response possibly by arresting terminal differentiation of B lymphocytes into immunoglobulin-secreting cells and there is some evidence that OKT8 positive T (T8+) lymphocytes are involved. These observations suggest that the regulation of the lymphocyte response by MO is a complex phenomenon in which the ratio of functional different subsets may be important. This may be critical for understanding the altered function of MO in human diseases. Our previous observations suggest that MO of some cancer patients possess an increased suppressor activity, and the presence of suppressor MO is a favourable prognostic factor. A further delineation of functional MO subsets should facilitate a better understanding of the role of MO in immunoregulation.

Antibodies, Anti-Idiotypic↗
PubMed1985

Involvement of I-J epitopes in the self- and allo-recognition sites of T cells: blocking of syngeneic and allogeneic mixed lymphocyte reaction-responder cells by monoclonal anti-I-J antibodies.

Monoclonal anti-I-Jk antibodies (mAbs) were found to inhibit syngeneic and allogeneic mixed lymphocyte reactions by blocking the responder T cells but not the stimulator cells. Only the responses of H-2k and H-2a strains were inhibited. Three different anti-I-Jk mAbs (1G8, 4B11, and KN34) showed different inhibitory patterns in allogeneic mixed lymphocyte reactions of individual H-2k strains, depending on the H-2 and immunoglobulin heavy chain variable region (IgVH) genes possessed by the stimulator strains. The results indicated that I-J epitopes are involved in the self- and allo-recognition sites of T cells, which are clonally distributed and used to recognize Ia plus IgVH-linked products.

Animals↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

"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↗
PubMed1982

"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↗
PubMed1982

The Fc receptors of normal and cancer patients monocytes.

The ability of human monocytes from normal donors and gastric-cancer patients to form rosettes with "O" Rh+(D) human erythrocytes coated with hyperimmune IgG anti-D antibody (EAhu) and to kill the same target in antibody-dependent cellular cytotoxicity (ADCC) were assessed. Trypsin pretreatment of normal monocytes decreased their ability to form rosettes with EAhu complexes, but their ADCC activity was unaffected. The Fc receptor (FcR) expression and ADCC activity of monocytes of cancer patients were elevated, and trypsin-treatment led to their further increase. The elevated values were related to the presence of the tumour. These results may suggest that human monocytes possess trypsin-sensitive and trypsin-resistant Fc receptors. The trypsin-resistant FcR seems to be involved in ADCC phenomenon and to be preferentially expressed on monocytes of some cancer patients.

Adult↗
PubMed1982

Isolation of human monocytes by rosetting with antibody coated human erythrocytes and isopycnic gradient centrifugation.

Human erythrocytes O,Rh+ (D) coated with hyperimmune human anti-serum formed rosettes primarily with monocytes in peripheral blood mononuclear cell suspensions. The rosetting cells (EAhu-FRC), separated on a Lymphoprep gradient were found in the pellet and were up to 95% pure monocytes as judged by cytochemical criteria. A two step procedure involving depletion of T lymphocytes followed by the isolation of EAhu-RFC yielded monocytes up to 98% pure. The isolated cells did not respond to mitogens in vitro, but they act as accessory cells in mitogen-induced T lymphocyte proliferation. This simple method may be useful in studying monocyte function in human disease as it does not require a large amount of blood.

Adult↗
PubMed1980

Activation of human monocytes for nitroblue tetrazolium reduction and the suppression of lymphocyte response to mitogens.

Human peripheral blood mononuclear cells freed from polymorphs reduce nitroblue tetrazolium (NBT). This reduction is due to monocytes, i.e. adherent, phagocytic, esterase-positive cells with Fc receptors. Monocytes allowed to phagocytose zymosan show increased NBT reduction which under optimal conditions is 12.2 +/- 2.4 x 10(-9) mol . hr-1 . 10(-6) monocytes. Monocytes which have phagocytosed zymosan depress the mitogen response of human lymphocytes to PHA. This effect of 'activated' monocytes is due to a soluble inhibitory mediator which appears in the supernatant after culture for 24 hr. Its appearance requires protein synthesis. It is suggested that NBT reduction of peripheral blood mononuclear cells can be used as a test for the state of monocyte activation in disease. The possibility that activated monocytes may depress blast transformation in vitro in disease states is discussed.

Cell Adhesion↗
PubMed1978

Monocyte changes in cancer patients and their role in mitogen induced lymphocyte responses.

Monocyte Fc receptor expression and monocyte-mediated antibody dependent cell cytotoxicity (ADCC) was studied in a group of patients with stomach and colorectal carcinoma. Is was found that FC receptor expression and ADCC was increased in patients as compared to control subjects. These differences were more evident after trypsin pretreatment of monocytes. There was an inverse correlation between these changes and lymphocyte response to PHA. The role of monocyte functional changes in determining the magnitude of patients' lymphocyte response is discussed.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

I-J epitopes are adaptively acquired by T cells differentiated in the chimaeric condition.

I-J has been defined as a locus mapped in the murine major histocompatibility complex (MHC) which encodes serological markers found primarily on the surface of suppressor T cells (TS) and soluble suppressor factors (TSF). Recent studies have, however, revealed that there is no such specialized locus within the MHC at the DNA level. As the existence of I-J determinants at the protein level on functional T cells, T-cell clones and hybridomas has been confirmed by several serological and biochemical studies, this contradiction has raised serious arguments in the immunological community concerning the nature, origin and expression of I-J determinants. We have raised a number of monoclonal antibodies against the polymorphic structure of I-J molecules, and have studied the expression of I-J epitopes on T cells derived from irradiated bone marrow chimaeras in which stem cells of different genotype differentiated into T cells under the foreign host MHC environment. The results, presented here, indicate that I-J epitopes are not primarily determined by the MHC genes of the stem cells themselves, but are adaptively acquired by T cells differentiated in the chimaeric condition according to the environmental MHC phenotype. Thus, the serologically detectable I-J epitopes are found to be associated with inducible T-cell receptors recognizing self class II MHC antigens.

Animals↗