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Biomedical subjects

M Zembala

Publications and source records attributed to M Zembala.

At least 127 records · Page 7Linked to original sources
PubMed1988

The altered expression of MHC-class II determinants on monocytes of cancer patients.

The expression of MHC class II determinants Ia.7 (detected by cross reactive mouse anti-Iak antibody) and HLA-DR on monocytes (MO) of gastric and colorectal cancer patients was examined. An increased proportion of MO bearing the Ia.7 determinant was found, while the number of MO expressing DR was not elevated. In gastric cancer patients the increased expression of the Ia.7 determinant was most pronounced in advanced cancer (stage IVA and IVB). The increased expression of this determinant was related to the presence of the tumour as the number of MO expressing Ia.7 decreased 6 months following surgical resection of the tumour. Further, the increased expression of Ia.7 on MO correlated with the tumour infiltration of the serosa. The Ia.7 determinants were mainly expressed on MO which also expressed the receptor for the Fc part of immunoglobulin. Immunostaining in cellular infiltrates surrounding the tumour revealed that Ia.7+ macrophages (MO) were more numerous than in normal gastric mucosa and severe chronic gastritis and were mostly present in close proximity to tumour cells, while DR+MO were mainly localized within the stromal tissue of the tumour and their number was not increased in cancer infiltrates. These observations indicate that the Ia.7+ subpopulation of MO may be involved in the anti-tumour response of the host.

Epitopes↗
PubMed1988

A alpha and A beta class II I-A determinants of antigen-specific T-helper factor and its antigen-nonbinding chain.

Antigen-specific T-helper factor (ThF) of CBA (H-2k) origin in the picryl (TNP) contact sensitivity system (Mr 60-70 kDa) was reduced with dithiothreitol under mild conditions. Affinity chromatography on antigen yielded an antigen-binding chain (Mr 20-30 kDa) and an antigen-nonbinding chain (Mr 40-50 kDa). Both chains were glycoproteins and were bound by lentil lectin. Affinity chromatography on anti-I-A monoclonal antibodies showed that I-A determinants occurred on the complete molecule and on the antigen-nonbinding, but not on the antigen-binding, chain. In contrast, five different monoclonal antibodies to I-E alpha failed to absorb ThF. Moreover, the complete molecule and the I-A+ antigen-nonbinding chains had determinants of the alpha and beta chains of I-A and conformational determinants which are based on both chains. Sequential absorption and elution showed that A alpha and A beta determinants occurred on the same molecular complex. These data suggest a minimal model of ThF as a two-chain disulfide-bonded structure with an antigen-binding chain and a separate I-A+ antigen-nonbinding chain which behaves as a single unit in phosphate-buffered saline and has elements of both A alpha and A beta.

Animals↗
PubMed1988

IL-2 influences the balance between immunity and unresponsiveness in the picryl (TNP) contact sensitivity system by blocking the development or action of an Lyt-2+, I-J+ T suppressor cell.

Mice injected with antigen (picrylated spleen cells) intravenously fail to develop contact sensitivity. However, contact sensitivity occurs if these mice are injected with IL-2. This effect of IL-2 was reproduced in vitro by taking spleen cells 2 days after injecting antigen intravenously and culturing them with either 150 u/ml recombinant IL-2 for 2 days or by pulsing with 600-1200 u/ml IL-2 at 4 degrees C for 1 hr. After 2 days in culture these antigen-exposed cells transfer contact sensitivity to naive recipients in a 24-hr experiment. However, the ability of antigen-exposed cells, pulsed with IL-2, to transfer contact sensitivity is abolished when they are incubated with unpulsed antigen-exposed cells and as few as 1/16 of their number have a significant effect. This phenomenon is specific, as normal cell or cells from mice injected with oxazolonated cells intravenously have no effect. The suppressor cells were Thy-1+, Lyt-1-, 2+, I-J+ T cells. It was concluded that IL-2 prevents the development/action of antigen-specific T suppressor cells.

Animals↗
PubMed1988

Immunoregulation of lymphoproliferation in vitro by monocytes and their subpopulations. I. The induction of suppressor T cells in long term cultures and the role of MHC class II determinants and preliminary characteristics.

Peripheral blood monocyte (MO) subpopulations isolated on a basis of functional expression or a lack of Fc receptor (FcR+ and FcR- MO) were used to study the regulation of the antigen (PPD)-driven lymphoproliferation. Long-term cultures of T lymphocytes with FcR+ MO, but not FcR- MO, led to the induction of T suppressor (Ts) cells that inhibited antigen-driven lymphoproliferation in the test cultures. These Ts cells were resistant to mitomycin C, belonged to afferent-acting category of Ts cells, expressed CD8 and HLA-DR determinants, and showed no antigenic specificity nor genetic restriction in action. The expression of MHC class II molecules (HLA-DR and HLA-DP but not HLA-DQ determinants) on MO which were used for antigen presentation was critical for Ts cell induction. It was concluded that specialized MO subpopulations may regulate the lymphoproliferation by inducing Ts cells (or Ts cell circuit) that in turn inhibit antigen-driven immune response.

Cells, Cultured↗
PubMed1988

Juvenile rheumatoid arthritis. Monocyte dysfunction in selected patients.

The in vitro parameters of cell-mediated immunity were studied in 20 children with an established diagnosis of Juvenile rheumatoid arthritis (JRA) (age range 4-15 years) and 23 age- and sex-matched healthy children. (No attempt was made to correlate the observed changes with clinical course or treatment). We are not certain, at this time, of clinical relevancy or the generalizability of the findings. The normal level of T-lymphocytes (CD3+) and normal proportions of CD4+ and CD8+ lymphocytes were seen in children with JRA. The in vitro response of lymphocytes to T-cell mitogen phytohemagglutinin (PHA) also was normal. The suppressor activity of JRA monocytes was essentially the same as controls. In contrast, monocytes from patients with JRA showed the following: decreased expression of receptors for Fc part of IgG immunoglobulin (FcR), diminished nitro blue tetrazolium (NBT) reduction activity, and depressed expression of Ia.7 major histocompatibility complex (MHC) class II determinants. This indicates that certain monocyte functions in selected patients with a variety of manifestations of JRA are depressed.

Adolescent↗
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

Nonspecific T suppressor factor (nsTsF) cascade in contact sensitivity: nsTsF-1 causes an Ly-1+2- I-A+ immune T cell to produce a second, genetically restricted, nsTsF-2.

We studied the mode of action of the nonspecific T suppressor factor (nsTsF-1) made in the picryl (TNP) system when T acceptor cells armed with antigen-specific TsF are triggered by antigen in the context of I-J. This suppressor factor does not inhibit the passive transfer of contact sensitivity directly, as shown by its failure to inhibit passive transfer by immune cells deprived of I-A+ cells. Its immediate target is an immune, antigen-specific, Ly-1+2-, I-A+ T cell. This cell, which may be regarded as a T suppressor effector cell (Ts-eff-2), produces nsTsF-2 when exposed sequentially to nsTsF-1 and antigen. This nsTsF subsequently inhibits the passive transfer of contact sensitivity. The action of nsTsF-2 is MHC genetically restricted. As the nsTsF-2 bears I-A determinant(s), this raises the possibility that it may act by combining with the recognition site for I-A on the T cell that mediates contact sensitivity.

Animals↗
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

Nonspecific inhibitor of DNA synthesis elaborated by T-acceptor cells. II. Requirements for its production and action.

The production of a nonspecific inhibitor of DNA synthesis (nsINH) appears to be one of the final events in the T-suppressor cell circuit in mice exposed to contact sensitizers. We report here that: The nsINH suppresses the proliferative response to a polyclonal T-cell mitogen, concanavalin A (Con A), regardless of the dose of Con A used. It also suppresses DNA synthesis in lymphoid cells stimulated with alloantigens. This suppression can be completely eliminated by adding exogenous interleukin 2 (IL-2). DNA synthesis in lymphoid cells exposed to nsINH before the proliferative stimulus is uninfluenced so that activation of the lymphoid cells at the same time as exposure to nsINH seems to be a requirement for its action. Since the activity of nsINH can be absorbed by activated Lyt-1+ or Lyt-2+ lymphocytes, the early activated T cell appears to be a target of the action of nsINH. The production of nsINH is abolished or severely reduced by adult thymectomy. Natural killer (NK) cells are resistant to nsINH action and no interferon (IFN)-like activity can be demonstrated in nsINH preparation using a conventional assay for IFN.

Animals↗
PubMed1986

Human T cell subsets differ in their ability to migrate in vitro and to produce T cell migration inhibitory factor.

The spontaneous migration in vitro, production of T cell migration inhibitory factor (TIF) and the response to TIF of OKT4+ and OKT8+ human T cell subsets were studied. The OKT4+ lymphocytes migrated far better than the OKT8+ cells although the movement of both subsets was comparably inhibited by TIF. The OKT8+ subset was found to be a major source of TIF, while OKT4+ cells were responsible for macrophage migration inhibitory factor (MIF) production. The implications of lymphokine production by OKT8+ cells for the regulation of inflammatory responses are discussed.

Antibodies, Monoclonal↗
PubMed1986

An overview of T-suppressor cell circuits.

This review gives an overview of two main suppressor circuits. In its complete form, the first circuit form has an early acting Ts-inducer that behaves like a T-helper cell for the production of idiotype-directed Ts-transducer or antigen-directed Ts-effector cells. In this circuit, the T-suppressor effector cell (Ts-eff) produces antigen-specific T-suppressor factor (TsF). This has a mode of action through the T-acceptor cell (T-acc), a cell that requires immunization, but not specific immunization, for its production. This cell, when armed with TsF-eff and then triggered with antigen and I-J, releases nonspecific TsF that blocks the passive transfer of contact sensitivity. It also blocks the production of IL-2. The biological significance of the complexities of this circuit is discussed in relation to the control of unresponsiveness and the handling infection and antigenic variation of microorganisms. The second set of suppressor cells, T suppressor afferent cells, inhibits only when given early in the immune response but differs from the Ts-inducer by lacking an obligatory mode of action through the Ts-eff/T-acc circuit. In general, the antigen-specific T-helper and T-suppressor factors have a two-chain disulfide-bonded structure. One chain carries the antigen-binding site and the other chain MHC-related determinants. Both chains are required for biological activity, and the genetic restriction in this complementation implies that the antigen-binding chain has a recognition site for MHC determinant(s). The generalization can be made that the MHC-related determinants carried by the factors and the genetic restriction in their induction, in their action, and in the interchain complementation between their separated chains all map to the same region of the genome. This is intelligible on the assumption that the T-cell receptor on the cell that produces the factor has a recognition site for antigen and MHC determinants and that the antigen-binding chain of secreted factor has the same properties.

Animals↗
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↗
PubMed1986

Immunological reactivity in children with Wilms' tumor.

Cellular immune reactivity was investigated in 49 newly diagnosed children with Wilms' tumor and compared to age-matched control. The level of total T (T4 degrees) and B lymphocytes was normal while the relative number of T lymphocytes with high affinity receptors for sheep erythrocytes (T29 degrees) was significantly decreased in the patients studied. The lymphocyte response to PHA in vitro was diminished but PHA-induced lymphokine production was not altered. The depression of T29 degrees level and lymphocyte reactivity to PHA was associated with high grade tumor rather than with the clinical stage. Lymphocytes of 42-47% patients reacted with autochthonous and allogeneic KCl tumor extracts in the migration inhibition test and the degree of reactivity was related to the histological differentiation of the tumor.

B-Lymphocytes↗
PubMed1986

Monocyte regulation of lymphokine production in cancer patients.

The effect of monocytes from patients with gastric cancer on lymphokine production was investigated. Patients' monocytes both augmented and reduced production of T-cell migration inhibitory factor (TIF) by normal and patients' T lymphocytes stimulated with PHA, while normal monocytes did not change or decreased the TIF production. This regulatory effect of cancer patients' monocytes on lymphokine production was independent of the initial potential of T cells to produce TIF. These observations suggest that the regulation of lymphokine production by monocytes is altered in some cancer patients.

Cell Migration Inhibition↗
PubMed1985

I-A region genetic restriction in the production and action of an antigen-specific T-helper factor which bears I-A region determinant(s).

Antigen-specific T-helper factor (ThF) augments the contact sensitivity reaction induced by the injection of small numbers of picrylated cells into mice. ThF was produced by injected picrylated spleen cells into the footpads and taking the 24-hr culture supernatant of the regional lymph node cells. Analysis showed that there was a genetic restriction in the induction of ThF, between these picrylated cells and the mouse making the ThF, which maps to the I-A region. This finding suggests that the receptor on the T cell which makes ThF, and by implication ThF itself, bears recognition site(s) for both antigen and I-A. ThF was then prepared from mice painted on the skin with picryl chloride, and the genetic restriction in its action was investigated. There was a requirement for genetic matching between the mouse producing the ThF and the final recipient which mapped to the I-A region. The genotype of the picrylated cell used as a source of antigen was unimportant. This I-A genetic restriction, together with the finding that ThF bears at least some I-A determinants, suggests that ThF may act by binding to the picrylated cells used as a source of antigen through its antigen-binding site and hence provide the I-A determinants needed for the recognition of antigen in the context of self-MHC. The present findings add to the list of antigen-specific factors which have a two-chain structure and show genetic restriction in their induction, action, and in the interaction between their chains which maps to the same region as the MHC-related determinant(s) which they bear.

Animals↗
PubMed1985

The regulation of polyclonal immunoglobulin synthesis by FcR+ and FcR- monocyte subsets.

FcR+ and FcR- monocyte subsets were added to the pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I-stimulated cultures of peripheral blood mononuclear cells (PBMC) or to PBMC depleted of monocytes. The numbers of immunoglobulin-secreting cells (ISC) and cells with intracytoplasmic immunoglobulins (PC) were evaluated 6 days later. The addition of FcR- subset increased the number of ISC in cultures of PBMC stimulated with PWM and reconstituted the response of monocyte depleted PBMC. In contrast, FcR+ monocytes suppressed PWM-induced response and, when added in high dose, also that induced by S. aureus. The FcR+ monocytes suppressed the response by inhibition of immunoglobulin secretion but not the development of PC. This suggests that FcR+ monocytes may modulate humoral response by preferential inhibition of the final differentiation of B lymphocytes into ISC.

B-Lymphocytes↗