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M Papiernik

Publications and source records attributed to M Papiernik.

At least 55 records · Page 3Linked to original sources
PubMed1987

Control of prothymocyte proliferation by thymic accessory cells.

All thymocyte subpopulations derive from intrathymic precursors which are double negative (DN) for Lyt-2 and L3T4 differentiation antigens. Although nearly half of DN cells express a receptor for interleukin 2 (IL 2R), they respond poorly to IL 2. DN cell proliferation can be obtained in the presence of various exogenous stimuli, but the in vivo signal for DN cell response to IL 2 remains unclear. We show in the present report that phagocytic cells of the thymic reticulum are able to induce the proliferation of DN thymocytes in the presence of recombinant IL 2 (rIL 2). Cell-to-cell contact is needed for this effect. Antibodies directed against class I MHC antigens but not against class II can inhibit DN cell proliferation. DNA-synthetizing cells were labeled by incubation with 10 microM bromodeoxyuridine either before or at various times during the culture period. Bromodeoxyuridine was then detected in the DNA of proliferating cells and/or their progeny already stained with anti-Lyt-2 and L3T4 antibodies. During the initial 16 h and independently of culture conditions, 16-25% of the cells expressed surface antigens and 50-65% of them derived from DN cells which were in S phase just before culture; these differentiated cells had a very short life span. In the second culture period, the presence of both rIL 2 and thymic accessory cells was necessary for cell survival. In these conditions, DN cell number and proliferation rate were constant and a low number of Lyt-2+ and/or L3T4+ cells was continuously generated. Thymic accessory cells therefore appear to provide the signal(s) necessary for IL 2-induced proliferation of thymocyte precursors. Implications of these findings for normal in vivo intrathymic proliferation and differentiation are discussed.

Animals↗
PubMed1987

Con A response and interleukin 2 receptor expression of thymocytes rosetting with phagocytic cells of the thymic reticulum.

Thymocytes bind to the phagocytic cells of the thymic reticulum (P-TR) and spontaneously forming rosettes were isolated and characterized. Rosetting thymocyte subsets included cells expressing different surface phenotype: most of them (91%) were of the double positive L3T4+ Lyt-2+ phenotype; a minor subpopulation (2.4%) expressed the helper L3T4+ Lyt-2- phenotype and finally a small subpopulation (6.3%) was negative for both L3T4 and Lyt-2 markers. Although the rosetting thymocytes were not enriched in mature single positive cells as compared to the non rosetting population, they showed a higher responsiveness to ConA plus recombinant IL-2. Moreover the rosetting thymocytes were induced to express IL-2 receptors just after stimulation with ConA whereas co-stimulation with ConA plus IL-2 was essential for the generation of IL-2 receptors on the non rosetting and total thymocytes. The possibility that the rosetting thymocytes acquired this activity during the rosetting process is discussed.

Animals↗
PubMed1986

Regulation of thymocyte proliferation and survival by deoxynucleosides. Deoxycytidine produced by thymic accessory cells protects thymocytes from deoxyguanosine toxicity and stimulates their spontaneous proliferation.

Deoxyguanosine (dGuo) inhibits thymic blast DNA synthesis and then induces thymocyte cell death. The dGuo inhibitory action, measured with four different assays (spontaneous thymidine incorporation, immunofluorescent detection of 5-bromodeoxyuridine incorporation, dye exclusion, tetrazolium salt cleavage), was suppressed in the presence of supernatants from cultures containing phagocytic cells. In particular, we studied the anti-dGuo activity in supernatants from thymic reticulum cultures (TRS) and in those from phagocytic cells isolated from TR cultures (P-TR). The anti-dGuo substance was identified as deoxycytidine (dCyd) by high performance liquid chromatography and other physicochemical studies. Secretion of dCyd by P-TR is accompanied by thymidine but not by purine nucleoside secretion. A dual mechanism of thymocyte rescue by dCyd was demonstrated by a study of the dose-dependencies of dCyd-mediated prevention and reversal, respectively, of the dGuo inhibition. In addition to this exogenously added anti-dGuo action, dCyd and dCyd-containing TRS induced significant stimulation of spontaneous thymic blast proliferation, and the kinetics of both effects were identical. These findings might suggest that a major role of thymic phagocytic cells is the supply of pyrimidine nucleosides to thymocytes resulting in the maintenance of proliferation and protection of at least some thymic blasts from the toxic effects of dGTP accumulation. The role of this system in the intrathymic selection process is discussed.

Animals↗
PubMed1986

Control of Ia antigen expression on phagocytic cells of the thymic reticulum by interferon-gamma and prostaglandins.

Phagocytic cells of the thymic reticulum (P-TR) spawned in the microenvironment of primary thymic stroma cultures express class II antigens on their membranes. We can show that Ia-antigen expression is regulated by the local secretion of interferon-gamma (IFN-gamma): (a) early primary culture supernatants contain IFN as tested by a cytopathogenic inhibition test after concentration of IFN activity; (b) the addition of a specific anti-IFN-gamma antiserum to primary cultures reduces Ia expression on P-TR suggesting that IFN-gamma produced in situ is implicated in Ia expression; (c) the percentage of Ia+ cells declines as primary cultures age. This phenomenon parallels the disappearance of thymocytes which are the supposed candidate for IFN-gamma secretion. (d) When isolated from their stromal environment and replated in secondary cultures, P-TR lose their membrane Ia antigen which can be re-expressed in the presence of recombinant IFN-gamma, but not IFN-alpha/beta. The decline of Ia expression on P-TR during the aging of primary cultures may be delayed by the inhibition of prostaglandin secretion.

Animals↗
PubMed1986

Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced by the coculture. Cooperation with medullary mature thymocytes or the presence of active Ia- accessory cells possibly able to convert to Ia expression during coculture experiments may account for these results.

Animals↗
PubMed1986

Increased Con-A-induced thymocyte proliferation and de novo Qa-2 antigen expression in Qa-2-depleted thymocyte cultures.

We have recently shown that thymocyte activation is associated with a strong increase of Qa-2 antigen expression. Contrary to what could be predicted from these results, the initial depletion of Qa-2+ cells from PNA- thymocytes increases the Con-A-induced proliferation. Qa-2+ cells not only reappeared after activation, but were enhanced in Qa-2-depleted PNA- cells compared to the control. The newly formed Qa-2+ population contained a higher percentage of Lyt 1+2- cells and thus seems to be different from the Qa-2+ pool initially present.

Animals↗
PubMed1985

Opposite effects of a glucocorticoid and an immunostimulating agent on prostaglandin production by two different cell types.

Studies were performed to investigate the effects of several agents known to modulate wound healing on prostaglandin production by mouse embryo fibroblasts and adult thymic phagocytic cells in culture. Dexamethasone (10(-6)M) induced in both cell types a significant inhibition of the production of PGE2 and 6 keto PGF1 alpha, and a moderate inhibition of PGF2 alpha. Using an antiglucocorticoid compound, RU 38486, we were able to demonstrate that the inhibition of PG secretion represents a classical receptor-mediated effect of the steroid. In contrast, LPS and RU 41740 (5 micrograms/ml) induced a significant stimulation of PGE2 and 6-keto-PGF1 alpha secretion in the two types of cells. These results suggest that agents which modulate in different ways the process of tissue repair have opposite effects on PG production by cells involved in inflammatory and/or immunological reactions.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Thymic reticulum in mice. IV. The rosette formation between phagocytic cells of the thymic reticulum and cortical type thymocytes is mediated by complement receptor type three.

A phagocytic cell of the thymic reticulum (P-TR) with dendritic shape recently has been isolated and characterized. We have previously shown that P-TR have an important role to play in the constitution of the thymic microenvironment. Indeed, P-TR are able to produce interleukin 1 and prostaglandin E2, both of which regulate thymocyte activation and proliferation. They are able also to stimulate the proliferation of syngeneic thymocytes enriched in the medullary type. In the present paper, we analyze a close relationship which exists between P-TR and thymocytes of the cortical type. About 25% of P-TR are able to bind to thymocytes and to form rosettes. Rosetting thymocytes represent about 5% of the total population and are PNA+, Lyt 1+2+, H-2-, and sensitive to in vivo steroid treatment. Pretreatment of P-TR with anti-Mac-1, a monoclonal rat IgG antibody against mouse macrophages and specific for complement receptor type three (CR3), abolished rosette formation. Rosette formation also was found to be inhibited by zymosan-treated serum containing the CR3 ligand, C3bi, and by certain sugars, in particular, N-acetyl-D-galactosamine and L-xylose. Our results suggest that rosetting thymocytes bind to CR3 on the P-TR membrane and that sugar constituents of the carbohydrate moieties on the thymocyte surface may serve as a recognition site during the binding process.

Animals↗
PubMed1985

Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids.

The production of prostaglandins by phagocytic cells of the thymic reticulum in culture (P-TR) was studied by using high pressure liquid chromatography and radioimmunoassay. Radioimmunologic determinations showed that thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) were the major compounds released into the culture medium, whereas prostaglandin F2 alpha (PGF2 alpha) was only a minor component. Indomethacin and dexamethasone exerted a similar pattern of differential inhibition of the secretion of prostanoids. PGE2 and 6-keto PGF1 alpha productions were markedly decreased by these anti-inflammatory drugs, whereas those of TXB2 and PGF2 alpha were not or were only slightly affected. Experiments performed with an antiglucocorticoid compound (RU 38486) showed that the steroid-induced inhibition of prostanoid secretion is a classical receptor-mediated action. These results demonstrated that phagocytic cells of the thymic reticulum, which resemble the thymic interdigitating cells, produce several types of prostaglandins. Because it has been described that P-TR regulate thymocyte proliferation in vitro via the secretion of both interleukin 1 and PGE2, these results suggest that anti-inflammatory agents may be able to modulate the thymic microenvironment and, consequently, thymocyte proliferation.

Animals↗
PubMed1984

Thymic lymphocytes. II. Phenotypic modifications of thymocytes after concanavalin A stimulation in the presence of interleukin 2: early modifications of Lyt 1+2+ subset and later proliferation of cells with more mature phenotypes.

Cortical thymocytes are devoid of any immune function, as tested by presently available techniques. The ability of this subpopulation to respond to mitogens or antigens in the presence of interleukin 2 (IL-2) produced by activated mature T lymphocytes has been claimed but is still questioned. In an attempt to study the participation of the different thymocyte subsets and especially that of the cortical type, phenotypic modifications were examined during concanavalin A activation in the presence of IL-2. An immunofluorescent double labeling technique with anti-Lyt 1 and anti-Lyt 2 antibodies was used which led to the determination of four different phenotypes: Lyt 1+2+, Lyt 1+2-, Lyt 1-2+, and Lyt 1-2-. Careful analysis of cell viability in culture and expression of the results in absolute numbers of living cells per culture allowed us to follow modifications of small cellular subsets. Cultures of total thymocytes and PNA-agglutinated (enriched in Lyt 1+2+ cells) and non-PNA-agglutinated cells (enriched in Lyt 1+2-, Lyt 1-2+, and Lyt 1-2- cells) were studied. It was shown that thymocyte activation began by early phenotypic modifications which took place within the first 2 hr of culture but only when Con A plus IL-2 were used. These modifications imply the reduction of the Lyt 1+2+ pool and a compensatory enhancement of Lyt 1-2+ and Lyt 1-2- cells, without modification of the total cell number or [3H]thymidine incorporation. These early phenotypic changes are interpreted as the modulation of antigens on the surface of Lyt 1+2+ cells. The second phase of thymocyte activation implies cell death (essentially Lyt 1+2+ cells) and cell proliferation. The cells which specifically proliferate in the presence of Con A and IL-2 are Lyt 1+2- and Lyt 1-2+, the latter always being present in greater number. Cell survival and absolute number of Lyt 1+2- and Lyt 1-2+ cells in the activated PNA- -enriched population are always higher than in total thymocyte and PNA+ cells cultures. Thus, if Lyt 1+2+ cortical thymocytes do not proliferate by themselves, they seem to intervene by providing Lyt 1-2+ cells which proliferate secondarily.

Animals↗
PubMed1984

Abnormal T-lymphocyte proliferation and cytotoxic responses induced by a neonatal injection of hydrocortisone: normalization by interleukin-2 addition.

Spleen cells from mice neonatally treated with hydrocortisone hemisuccinate (HHC) had an abnormal pattern of cell-mediated immunity when tested two weeks later. Mitogen-induced proliferation was reduced. The proliferative responses to allo-antigens were normal but the cytotoxic response thereby induced was impaired. The mechanisms of these anomalies are complex: reduction of cytotoxic precursors as measured by limiting dilution assays; enhancement of suppressor cells which are able to reduce the cytotoxic response of normal spleen cells; reduction of interleukin-2 (Il-2) production. The addition of exogenous Il-2 restores normal proliferative and cytotoxic responses.

Animals↗
PubMed1984

[The thymus micro-environment and T lymphocyte differentiation].

T cell precursors, which are derived from foetal liver and later from bone marrow, are obliged to colonize the thymus to differentiate into mature T cells. Multiple factors, secreted by cells of different types and origins, are involved in the constitution of a suitable micro-environment. Thymic epithelial cells have an endo-ectodermal origin, while the epithelial rudiment is secondarily colonized by mesodermal precursors of lymphocytes, macrophages and interdigitating cells. The migration of stem cells into the thymus is controlled by chemotactic factors which are derived from epithelial cells as well as from mature thymic medullary cells. Intra-thymic differentiation is controlled by thymic humoral factors secreted by epithelial cells. One of these factors, the "facteur thymique sérique" (FTS) (now called thymulin), has been isolated from the serum and also plays a role in the later extra-thymic maturation process. Thymic hormones are able to generate differentiation antigens on the surface of pre-thymic precursors. They have complex effects on the immunological function of post-thymic precursors. In addition to thymic hormones, other signals, such as interleukins, are necessary. Dendritic-shaped phagocytic cells of the thymic reticulum are able to secrete IL1 which is necessary for the secretion of IL2 by mature thymic medullary lymphocytes. MHC antigens on thymic epithelial cells and other factors, such as prostaglandins, also play important roles in intra-thymic T cell differentiation.

Animals↗
PubMed1983

Thymic reticulum in mice. II. Culture and characterization of nonepithelial phagocytic cells of the thymic reticulum: their role in the syngeneic stimulation of thymic medullary lymphocytes.

In the present report the characteristics of nonepithelial phagocytic cells of the murine thymic reticulum are described. Primary cultures were established from thymic fragments. Nonadherent cells with hairy membranes proliferated on the surface of established primary monolayers. These cells were recovered and replated in secondary cultures were they appeared as large adherent cells with dendritic shape. At the electron microscopic level, phagocytic cells of the thymic reticulum in culture (P-TR-C) appear as clear vacuolated cells with an indented nucleus and few lysosomes; this morphological aspect makes them different from the common macrophage, despite their phagocytic capacity. P-TR-C are positive for nonspecific esterase, acid phosphatase which is found in the few lysosomes present, 5'-nucleotidase and alpha-D-mannosidase, but negative for peroxidase. A high proportion of alpha-mannosidase-positive cells is inconsistent with the common macrophage, but in common with other cells with dendritic shape such as Langerhans cells. They are Thy-1-, Ig- and nearly half of them are IA+. P-TR-C can be defined as the stimulator cells for syngeneic stimulation; they are able to induce the proliferation of lymphocytes enriched in mature syngeneic medullary thymocytes, but not in immature cortical ones. Characteristics of P-TR-C make them very similar to the interdigitating cells described in the peripheral lymphoid organs and in the thymus in situ.

Animals↗
PubMed1983

Thymic reticulum in mice. III. Phagocytic cells of the thymic reticulum in culture secrete both prostaglandin E2 and interleukin 1 which regulate thymocyte proliferation.

A phagocytic cell of the thymic reticulum in culture (P-TR-C) has recently been isolated whose characteristics closely resemble those of the thymic interdigitating cell despite the modifications induced by culture conditions. In the present report it is demonstrated that this cell population is able to produce both interleukin 1 (IL 1) and prostaglandin E2 (PGE2). IL 1 has no direct mitogenic effect on thymocytes but is comitogenic with concanavalin A. PGE2 has no direct effect on the secretion of IL 1 by P-TR-C, but has an effect antagonistic to IL 1, inhibiting thymocyte proliferation. P-TR-C are thus able to modulate thymocyte proliferation in vitro.

Animals↗
PubMed1983

Modification of helper and suppressor/cytotoxic lymphocyte subsets in mice with motor end-plate disease.

Motor end-plate disease (Med) in mice is associated with complex immunological abnormalities which are shared by the heterozygous +/MedJ mice, which exhibit no or mild clinical manifestations, and by MedJ/MedJ mice which die from this neuromuscular disorder. In the present paper we extend our immunological data with the study of splenic lymphocyte subsets with Lyt monoclonal antibodies. Both MedJ/MedJ and +/MedJ 14-18 day old mice have high Lyt1+/Lyt2+ ratios, with higher Lyt1+ and reduced Lyt2+ lymphocyte pools as compared to normal mice. This correlates with the low suppressive function previously described, but is unexpected in view of the low helper function as measured by the response to SRBC immunization. Adult +/MedJ mice recovered normal T lymphocyte subset levels, while the small group of MedJ/MedJ mice that escapes death but continues to suffer from the neuromuscular illness maintains high Lyt1+/Lyt2+ ratios.

Animals↗
PubMed1983

Sezary syndrome. I. Specific skin-directed migration of peripheral blood lymphocytes.

The in vitro migration of peripheral blood lymphocytes (PBL) from Sezary syndrome (SS) patients and from controls was studied using a migration assay under agar. Only PBL from SS patients migrate to normal allogeneic skin. This migration is organ specific. It requires the integrity of lymphocyte membrane receptors. Serum factors are not involved. Studies of the nature of these migrating lymphocytes using monoclonal antibodies suggest that they belong to a subset of helper T cells. These data indicate a functional impairment of SS lymphocytes, which enables them to respond to a skin-derived signal.

Blood Physiological Phenomena↗
PubMed1982

Thymic hormone-containing cells. Characterization and localization of serum thymic factor in young mouse thymus studied by monoclonal antibodies.

The characterization and distribution of cells containing the serum thymic factor (FTS) in the thymus of young mice was studied by immunofluorescence using monoclonal anti-FTS antibodies. FTS+ cells were distributed throughout the thymic parenchyma but were more frequent in the medullary region than in the cortex. FTS-containing cells presented a stellate or globular aspect, and some of them exhibited fluorescent cytoplasmic granules. The epithelial nature of FTS+ cells was confirmed by double-labeling experiments using an anti-keratin antiserum (as an epithelial cell marker). Nevertheless, only a minority of keratin-positive epithelial reticular cells contained FTS. All controls, including the incubation of sections from nonthymic tissues with the anti-FTS antibodies, were negative. Taken together, these results confirm the exclusive localization of FTS-containing cells within the mouse thymus.

Animals↗