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J Pryjma

Publications and source records attributed to J Pryjma.

At least 55 records · Page 3Linked to original sources

Effect of dexamethasone on mechanisms responsible for regulation of polyclonal B-cell response.

The effect of dexamethasone (Dex) on the differentiation of pokeweed mitogen (PWM), or Staphylococcus aureus Cowan I (SAC)-stimulated human peripheral blood mononuclear cells (PBMC), into immunoglobulin secreting cells (ISC) was studied with special emphasis on the regulatory role of IL-2 in these systems. Dex, known to reduce endogenous IL-2 production and expression of IL-2 receptors, reduced the proliferation of pokeweed mitogen-activated T-cells, and the proliferation was restored by exogenous recombinant interleukin 2 (rIL-2). Furthermore, Dex enhanced in PWM and in SAC-stimulated cultures, the number of ISC. Addition of rIL-2 resulted in a further increase of ISC in SAC-stimulated cultures, whereas in PWM-stimulated cultures the enhancing effect of Dex was reversed. When IL-2 receptors were blocked by a monoclonal anti-IL-2 receptor antibody rIL-2 was no longer suppressive. Addition of monocytes to PWM-stimulated cultures resulted in suppression or the number of ISC, which was even more pronounced when monocytes were pretreated with rIL-2. In contrast to ISC, neither a suppressive effect of rIL-2 nor an enhancing effect of Dex was observed when PWM-stimulated cultures were evaluated for cells with intracytoplasmic immunoglobulin (plasma cells). From these results we conclude that Dex, by blocking IL-2 production and receptor expression, interferes with IL-2 mediated induction and/or activation of suppressor mechanisms.

B-Lymphocytes↗

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↗

Pokeweed mitogen activated suppressor T-cells preferentially reduce immunoglobulin secretion by differentiated B-lymphocytes.

In contrast to pokeweed mitogen (PWM), S. aureus Cowan I (SAC) does not activate suppressor T-cells in cultures of human peripheral blood mononuclear cells, although the SAC induced response leading to the appearance of immunoglobulin secreting cells (ISC) is suppressed by PWM activated suppressor T-cells. Therefore, cultures co-stimulated by SAC and PWM were chosen to find out which stage of the SAC triggered B-cell response is controlled by PWM activated suppressor T-cells. By incorporation of [3H]thymidine and determination of B-cell number in culture it was shown that neither PWM itself nor PWM induced suppressor T-cells interfere with SAC induced B-cell proliferation. The final stages of B-cell maturation were monitored by parallel evaluation of cells producing immunoglobulins (cells with intracytoplasmic immunoglobulins) and secreting them (plaque assay). It was shown that PWM activated suppressor T-cells reduce the number of ISC more effectively than the number of immunoglobulin producing cells, indicating that these two features of differentiated B-lymphocytes may be independently controlled.

Antibody-Producing Cells↗

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↗

Monocyte-T-cell interactions in the regulation of polyclonal B-cell response.

Human peripheral blood monocyte subsets with and without Fc receptor for human IgG are known to suppress (FcR+) and enhance (FcR-) pokeweed mitogen-induced polyclonal immunoglobulin synthesis in vitro. The ability of these subsets to modulate immunoglobulin production in the presence or absence of OKT8+ T cells and under conditions where suppressor T-cell activation was blocked by irradiation or mitomycin C was studied. It was shown that, regardless of the presence or absence of suppressor T cells, FcR+ monocytes can suppress immunoglobulin production if their number in culture exceeds 20%. However, at lower numbers this monocyte subset was suppressive only when suppressor T cells were activated. The suppressor T-cell activation was shown to be independent of the predominant presence of the FcR+ or FcR- monocyte subset. Moreover, the enhancing effect of FcR- monocytes was not caused by their interference with suppressor T-cell activation.

B-Lymphocytes↗

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↗

Immunoglobulin production of human lymphocytes stimulated by Staphylococcus aureus Cowan I and pokeweed mitogen: differential effects of recombinant interleukin-2.

The number of immunoglobulin-secreting cells (ISC) upon stimulation with pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I (SAC) in recombinant interleukin-2 (rIL-2)-supplemented cultures of human peripheral blood mononuclear cells (PBMC) and co-cultures of B and T cells was studied. It has been shown that the addition of rIL-2 to culture can enhance or depress the number of ISC depending on the polyclonal B-cell activator used for culture stimulation. The SAC-induced response was enhanced in the presence of rIL-2, while the number of ISC in PWM-stimulated cultures was depressed. Moreover, in cultures stimulated simultaneously by both activators, the suppressive effect of rIL-2 prevailed, indicating that the reported direct effect of the lymphokine on SAC-activated B cells cannot overcome the suppressive activity of PWM-induced suppressor T cells. rIL-2 could not activate suppressor T cells in the absence of PWM, and has no effect on the number of helper or suppressor cells in the culture.

Antibody-Producing Cells↗

Suppression of Staphylococcus aureus Cowan I-induced immunoglobulin synthesis in vitro: discrimination between the presence of suppressor T cell precursors and effectors.

In co-cultures with control cells lymphocytes obtained from some patients with hypogammaglobulinaemia can suppress PWM but not S. aureus Cowan I-induced polyclonal immunoglobulin production. When such co-cultures were stimulated at the same time with both mitogens, the response was greatly suppressed. This phenomenon was further studied in cultures of lymphocyte populations isolated from healthy donors. It was found that suppressor T lymphocytes activated by PWM in cultures co-stimulated with Con A, with high T:B cell ratio, or with an increased proportion of OKT8+ T cells can suppress the S. aureus-induced response. In contrast, under the same conditions S. aureus did not activate suppressor cells. Moreover, in cultures stimulated with this polyclonal B-cell activator OKT8+ lymphocytes could serve as helper cells.

Agammaglobulinemia↗

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↗

Studies of bronchial secretion. The influence of inflammatory response and bacterial infection.

Bronchial secretions obtained during bronchoscopic examination of 60 children suffering from respiratory tract infections were studied for the concentration of immunoglobulins, anti-proteolytic factors, lactoferrin, and lysozyme. Eleven children having bronchial asthma without a history of chronic or recurrent infections of the respiratory tract were designated as a control. The results were analysed in relation to clinical diagnosis (chronic bronchitis, bronchitis, bronchiectasis) or to the local status of bronchial mucosa at the time of bronchoscopy (no inflammation, inflammation, inflammation with documented bacterial infection). The statistical analysis of the results revealed a decrease of lactoferrin and locally produced IgA in the group of children suffering from bronchitis and chronic bronchitis. Samples infected with Haemophilus species had significantly higher concentration of lactoferrin than any other group. Similarly, albumin in this group was higher than in the other group except that other bacteria were present. Samples infected with Haemophilus also had increased concentrations of S-IgA, IgG, and anti-proteolytic factors when compared with the group without local inflammation.

Bacterial Infections↗

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↗

The use of Staphylococcus aureus Cowan I for evaluation of suppressor-T-cell activity in hypogammaglobulinemia: evidence for two functionally distinct suppressor T cells.

In coculture experiments with normal lymphocytes, peripheral blood lymphocytes (PBL) of 10 boys with hypogammaglobulinemia were screened for the presence of cells able to suppress Pokeweed mitogen (PWM)- and Staphylococcus aureus Cowan I-induced immunoglobulin production in vitro. PBL and T lymphocytes of two patients were shown to suppress reproducibly PWM-induced immunoglobulin production of control PBL and of control B + T lymphocytes. PBL of three other patients were also able to suppress but their activity was expressed only in combination with some but not other normal lymphocytes. In neither case was the Cowan I-induced response suppressed. PBL and T lymphocytes of one other patient were able to suppress both PWM- and S. aureus Cowan I-induced immunoglobulin production of normal lymphocytes. These data provide evidence for two functionally distinct suppressor T lymphocytes in hypogammaglobulinemic patients.

Agammaglobulinemia↗

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↗

Immunoglobulin production in cultures of human peripheral blood lymphocytes upon stimulation with various killed staphylococci.

Formalin killed Staphylococci (S. epidermidis, S. saprophyticus and six different strains of S. aureus) were used as inducers of immunoglobulin production in cultures of human peripheral blood lymphocytes. These strains differed in cell wall composition which raised a question what cell wall constituent is responsible for induction of the response. All strains except S. epidermidis induced the response in cultures of unseparated peripheral blood lymphocytes but only some of them were able to trigger immunoglobulin production in T-cell depleted cultures. The obtained results suggest that peptidoglycan is most likely responsible for stimulatory activity of Staphylococci while the presence of protein A reduces the T-cell dependency of the response.

Cell Wall↗

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↗

The evaluation of immune status in children with the past history of obstructive bronchitis.

Selected parametres reflecting cellular and humoral immunity were analyzed in 98, 10 year-old children, who had been hospitalized during first 2 years of life because of bronchitis. In this group, 46 children suffered from obstructive bronchitis and 52 from other types of bronchitis. Serum immunoglobulins, complement components, and antiproteolytic factor levels, T and B lymphocytes counts, leukocyte migration inhibition, and skin tests to PHA and Polyvaccine were compared and analyzed in relation to bronchial obstruction and allergic symptoms in early childhood. The results obtained did not show any significant difference when the group with obstructive type of bronchitis was compared to the rest of children studied. Some differences (increase of the percentage of EAC-FRC and decrease of the levels of the antiproteolytic factors) were noted in relation to allergic symptoms.

Asthma↗

Regulatory function of normal monocytes in the in vitro immunoglobulin production.

Induction of the immunoglobulin production by pokeweed mitogen (PWM) and S. aureus. Cowan I has been evaluated in cultures of human peripheral blood mononuclear cells gradually depleted of adherent cells. Partial depletion cells (monitoglobulins while almost complete depletion caused decreased production. These results suggest that an optimal balance of monocytes to lymphocytes is essential in the triggering of immunoglobulin production by human mononuclear cells (MNC) in vitro and that normal monocytes, when in excess, suppress in vitro differentiation of B lymphocytes into immunoglobulin secreting cells.

Antibody-Producing Cells↗

The T-dependent and T-independent humoral immune response in cobra venom treated mice.

The humoral immune response to T-dependent antigens (SRBC, DNP5BSA, DNP50BSA, DNP-KLH) and T-independent antigens (SIII, Levan, DNP-SIII, DNP-Levan) was studied by hemolytic plaque assay in mice depleted of C3 by Cobra venom treatment. Suppression of the immune response in C3 depleted animals was not restricted only to T-dependent response and also the response to some T-dependent antigens (DNP50-BSA, DNP-KLH) was not suppressed under conditions of the experiment. Results are discussed in relation to postulated exclusive role of C3 in the induction of T-dependent immune response.

Animals↗