Biomedical subjects

W Ptak

Publications and source records attributed to W Ptak.

At least 73 records · Page 4Linked to original sources

PubMed1986

Deficiency of contrasuppressor lymphocytes in alloxan-diabetic mice.

Ly 1 immune cells of alloxan diabetic mice are inferior to cells of normoglycemic PCl sensitized animals in transferring adoptive responses into recipients. A new regulatory activity, contrasuppression, that prevents suppressor cells from influencing activity of immune cells, has been recently described. Two types of Ly 1 contrasuppressor (Tcs) cells modulate contact sensitivity reactions in mice. A non-specific Tcs cell, which by itself has no immune activity, helps Ly 1 immune effector cells in adoptive transfer to bypass, in the recipient, the suppressor cell barrier. The antigen-specific Tcs cell induced by immune complexes makes Ly 1 effector cells resistant to specific suppression. Both Tcs cell, in contrast to Ly 1 effector cells, adhere to Vicia villosa lectin and can easily be separated (VV+ and VV-, respectively). Our experiments show that diabetic mice are deficient in nonspecific Tcs cells. The most important finding was that when immune Ly 1 cells of diabetic mice, which otherwise transfer little immunity, were injected together with Ly 1 VV+ cells of normoglycemic animals (these cells have no ability to transfer immunity whatsoever), the adoptive transfer was significantly augmented. We also demonstrate that diabetic mice are unable, upon appropriate immunization, to produce antigen-specific Tcs cells. Since a hypoinsulinemic environment abolishes the function of promiscuous Tcs cells and prevents the development of antigen-specific Tcs cells, this may suggest that contrasuppressor cells have insulin receptors which make them particularly sensitive to insulin deficiency.

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PubMed1986

Preferential induction of antigen-specific contrasuppressor T lymphocytes by trinitrophenyl (TNP)-substituted Langerhans cells.

We have tested the ability of trinitrophenyl (TNP)-labelled antigen-presenting cells (Langerhans cells (LC) and peritoneal macrophages (M phi)) administered intravenously to induce cells that mediate and regulate contact sensitivity. TNP-M phi fail to induce contrasuppressor cells (Tcs) but activate efferent T suppressor (Ts) cells. However, the activity of immune cells can be recovered after removal of Ly 2 Ts cells. In sharp contrast, TNP-substituted purified LC produced a significant contact sensitivity reaction, which is roughly equivalent to that achieved by skin sensitization with picryl chloride. Immune cells from these animals were relatively resistant to suppression by antigen-specific Ts cells, and we have found that their resistance is due to the presence of Ly 1, Vicia villosa lectin adherent, I-J+ cells. The Tcs cell induced by TNP-LC is indistinguishable by surface markers and function from Tcs cell found in mice injected with antigen-antibody complexes. Both these Tcs cells are capable of protecting immune cells from the effects of suppression by antigen-specific Ts cells if added in the proper sequence. Although they have identical surface phenotypes, it is not known at present whether or not Tcs cells induced by two different antigen presentations are identical. The possible reasons why LC are such potent inducers of contrasuppression are discussed.

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PubMed1986

Differential effect of experimental diabetes on the early and late phase of contact sensitivity reaction in mice.

Contact sensitization induces two different kinds of T cells (both Ly 1) that act in sequence to produce upon challenge with antigen a classical 24-hour local skin swelling reaction. One of these cells produces an antigen-specific factor. It has been suggested that it sensitizes mast cells, similar to IgE antibody, and causes them to release vasoactive amines in the presence of antigen. This results in an early (2-hour) swelling reaction. Increased vascular permeability facilitates the entry of the second, lymphokine-producing Ly 1 cell into the site of reaction to elicit the classical 24-hour delayed-type hypersensitivity reaction. In alloxan diabetic mice, contact sensitivity reactions are reduced significantly, and our experiments show that insulin deficiency affects only the activity of the late acting, lymphokine-producing cell and leaves the factor-producing cell responsible for the early swelling reaction unaffected. Our experiments demonstrate that insulin deficiency has different effects on distinct subpopulations of T lymphocytes.

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PubMed1985

Effect of surgical trauma (gastrectomy) on cell-mediated and humoral responses in mice.

Gastrectomy in mice affects the cell-mediated (CMI) and humoral immunity in a diverse fashion, such as CMI (contact sensitivity reaction) is severely impaired and antibody response is enhanced. Both effects are transient and disappear several days after surgery. While suppression of contact sensitivity is mediated by non-specific Ly 1-2+, L-J+ suppressor T cells generated by surgical stress, the mechanisms of enhancement of antibody response is unknown. We assume that the split unresponsiveness induced by surgical trauma has a clear survival advantage. Increased antibody production is the major defence mechanism against bacterial infections, while decrease of CMI prevents autoimmune response against altered (damaged) self structures.

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PubMed1985

Suppression and contrasuppression in the induction of contact sensitivity by the administration of cellbound antigen-antibody complexes.

The tolerogenic signal produced by the i.v. injection of haptenated peritoneal exudate cells can be converted to an immunogenic signal by treating the cells with antibody to the hapten before administration. We examined this phenomenon and found that immunity induced by antigen-antibody complexes, as opposed to skin sensitization, is resistant to suppressor T cell influences. This resistance to suppression is due to the activation of an I-J+, Ly-1 T cell population which adheres to the Vicia villosa lectin, all characteristics of contrasuppressor T cells. Because haptenated cells can induce immunity if injected subcutaneously or into cyclophosphamide-pretreated recipients (thereby avoiding the induction of suppressor cells), we suggest that the activation of contrasuppressor cells by antigen-antibody complexes overrides suppressive influences in the host, allowing immunity to become dominant. The possible roles of suppression and contrasuppression in channeling the effector arm of the immune response (e.g., contact sensitivity vs humoral immunity) are discussed.

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PubMed1984

Use of micrometers and calipers to measure various components of delayed-type hypersensitivity ear swelling reactions in mice.

The choice of the type of instrument to measure delayed-type hypersensitivity (DTH) in mice, as assayed by ear swelling reactions, influences the experimental results. When a caliper that applies little pressure to the ears is employed, DTH reactions in ears of mice sensitized to picryl chloride show an early onset at 2 h after challenge, comparable swelling at 4 h and a slow rise to a 24 h classical peak response thereafter. In contrast, 3 different micrometers that apply more pressure to the ears reveal a biphasic pattern of ear swelling reactions in mice immunized and challenged with picryl chloride. The early component of DTH measured by these micrometers peaks 2 h after challenge. Thereafter the measured ear thickness declines, and the onset of the classical delayed reaction is detected at 12 h after ear challenge. Yet another instrument, that in contrast to the caliper and micrometers mentioned above, applies all the pressure to only a very restricted area of the ear, fails to detect an early swelling reaction; the delayed reaction is first detected at 12 h after ear challenge and rises thereafter to a 24 h peak. The differences in outcome of the assays using the different instruments indicate that the early component or DTH reactions differs from the late component of DTH reactions in that the early swelling is easier to compress when pressure is applied by the instrument used for measurement. This is probably caused by the fact that the late reactions are due to a cellular infiltrate, whereas the early reactions are edematous in character, and are due to accumulation of plasma components.

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PubMed1984

The induction of oxazolone-specific T suppressor afferent cells in mice by hapten-modified isologous IgG.

Injection of isologous 4(ethoxymethylene)-2-phenyl-oxazolin-5-one (oxazolone; OX)-substituted thymocytes or OX-labeled IgG (OX-IgG) into mice produces specific unresponsiveness in which immunization with homologous (OX), but not heterologous (picryl chloride), hapten on the skin does not result in significant contact sensitization. However, while injection of OX-substituted thymocytes triggers suppressor cells which inhibit the effector stage of contact sensitivity reaction, OX-IgG induces cells which suppress exclusively the afferent stage of reaction. In contrast to OX-IgG, OX-substituted F(ab')2 fragments, IgM, and albumin are ineffective. T suppressor afferent cells have Ly-2 and I-J surface markers and their precursors are resistant to cyclophosphamide treatment and adult thymectomy. We assume that T suppressor afferent cells recognize antigen in conjunction with intact IgG molecules, although the exact mechanism is unclear.

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PubMed1984

Distinctive immunological properties of cultured murine thymic epithelial cells.

Skin painting with chemically reactive haptens induces a hapten-specific state of hypersensitivity that is long lasting and can be transferred to unirradiated recipient mice. A similar state of hapten-specific contact sensitivity can be induced by intravenous immunization with hapten-conjugated cells. Thus far, only two cell types have been described that can perform this function: Langerhans cells of the skin, and splenic dendritic cells. All other types, coupled with hapten, induce either tolerance or a short-lived state of contact hypersensitivity that is readily suppressed, and cannot be transferred to normal recipients. In the present experiments, it was demonstrated that culture-enriched, hapten-coupled thymic epithelial cells can also induce a state of stable contact hypersensitivity identical to that induced by skin painting. This provides evidence that thymic epithelial cells have distinctive properties as antigen-presenting cells in vivo. The relationship of this finding to the postulated role of thymic epithelium in T-cell development is discussed.

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PubMed1984

Induction of "allogeneic effect"-like reaction by syngeneic TNP-modified lymphoid cells.

TNP-substituted SRBC-immune spleen cells, when injected into cyclophosphamide-treated recipients, are recognized by T lymphocytes and produce, in the presence of specific antigen (SRBC), significantly more PFC than nonsubstituted cells. Labeling of immune B cells is more important in producing the augmented responses than is the labeling of immune T cells. TNP determinant has to be bound directly to the transferred immune cells to produce enhanced antibody responses, as when recipients were injected with non-substituted immune cells and TNP-substituted non-immune cells simultaneously, no increase in PFC number was noted (lack of a bystander effect). When recipients were rendered tolerant to TNP, two separate effects were observed, dependent on the mode of inducing unresponsiveness. In mice which were treated with TNP over an extended period of time, lack of recognition of TNP was demonstrated, such that TNP-substituted cells failed, when transferred, to produce an augmented response. When a short-term tolerogenic regime was used, the adoptively transferred TNP-labeled cells gave a very poor response (greater than 95% inhibition) due to in vivo suppression and/or killing. These results, together with the lack of influence of tolerance induced to unrelated hapten (DNP or OX), confirm the antigen specificity of the phenomenon. The reaction observed by us shows a striking resemblance with, but not identical to, the "allogeneic effect" produced by MHC encoded alloantigens. Our results extend the list of analogous immune reactions induced by MHC encoded alloantigens and TNP-derivatized self.

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PubMed1984

Production of antigen-specific contrasuppressor cells and factor, and their use in augmentation of cell-mediated immunity.

A single injection of TNP-labeled mouse gamma-globulin (TNP-IgG) can render the contact sensitivity response of mice resistant to suppressor cells (Tsc) and their biologically active cellfree products (TsF). Lyt-1 T cells of mice treated with TNP-IgG can protect the adoptive contact sensitivity response of immune cells from the antigen-specific suppressive effect produced by the addition of antigen-specific TsF or Tsc. When T cells of TNP-IgG-treated mice are put into culture, they produce an antigen-specific contrasuppressor factor (TcsF) that can replace the activity of the cells. When immune cells are preincubated in vitro with TcsF, they become refractory to Tsc and TsF added subsequently. The TcsF, however, has no ability to restore responsiveness to immune cells that had been previously exposed to TsF. The TcsF binds specifically to TNP, expresses an I-J-controlled determinant, and does not express standard determinants found on mouse Ig. The treatment that primes the contrasuppressor system to protect the contact sensitivity response also reportedly renders the antibody-producing system tolerant, (i.e., produces so called "split tolerance"). These results are discussed in light of the possibility that the contrasuppressor system can be responsible for so called isotype-specific immunity by rendering one arm of the immune system resistant to generalized suppressive mechanisms.

Animals↗

PubMed1984

Antigen-specific T contrasuppressor factor in cell-mediated immunity: interactions leading to eradication of the tolerant state.

Interactions between a T cell-derived, antigen-specific, contrasuppressor factor (TcsF) and immune T cells that block the action of T suppressor factors and allow the transfer of cellular immunity into tolerant recipients are described. Immune T cells from contact-sensitized donors are capable of transferring specific immunity into normal recipients but not into animals rendered tolerant to the specific antigen. Brief exposure of the immune cells to the TcsF enables the effective transfer of immunity into such tolerant recipients. In addition, treated immune cells become resistant to subsequent exposure to T suppressor factor (capable of inhibiting transfer of immunity to normal recipients). A cyclophosphamide-sensitive, I-J+, Ly-2 T transducer cell is required in the immune donor cell population for contrasuppression to be induced by the TcsF plus specific antigen. These cells release an antigen-non-specific contrasuppressive factor capable of rendering immune targets, depleted of transducer cells, resistant to suppression (either by suppressor factor or in the tolerant recipient). The results indicate that contrasuppression in contact sensitivity is antigen specific and that the balance of suppression and contrasuppression determines tolerance vs responsiveness in this system. The symmetrical resemblance of the contrasuppressive interactions to those of suppression in contact sensitivity are discussed.

Animals↗

PubMed1984

Characterization of two different Ly-1+ T cell populations that mediate delayed-type hypersensitivity.

This paper describes two functionally different T cell populations that mediate delayed-type hypersensitivity (DTH) reactions in contact-sensitized mice. Both of these T cells are Ly-1+, Qa-2-, and Vicia villosa lectin nonadherent. One of these T cell subpopulations is responsible for the classical 24- to 48-hr component of DTH reactions, is induced 3 to 4 days after immunization, is H-2 restricted, is sensitive to irradiation and to antigen-specific T cell-derived suppressor factors, and is found in nylon wool-nonadherent as well as nylon wool-adherent populations. In contrast, the T cell population that is responsible, via an antigen-specific T cell factor, for a recently described early component of DTH, which is an obligatory initial step for expression of DTH, is induced within 24 hr after immunization, requires much less antigen for immunization, is not H-2 restricted, is not sensitive to irradiation nor to T suppressor factors, and is found exclusively in the nylon wool-nonadherent fraction. These results support a new formulation of DTH. According to this formulation, Ly-1+ T cells produce an antigen-specific, tissue-sensitizing, mast cell-activating factor, and via this factor induce the early component of DTH, which is an obligatory first step in which local antigen challenge induces increased local vascular permeability. This required opening of gaps between endothelial cells is due to T cell factor-dependent release of the vasoactive amine serotonin from cells such as mast cells. This first step allows the second, H-2-restricted, Ly-1+ T cell population to enter the reaction site, and to then be triggered by antigen to release lymphokines that attract the subsequent influx of blood-borne, bone marrow-derived leukocytes to constitute the classical delayed-in-time component of DTH reactions.

Animals↗

PubMed1984

Mast cell activation and vascular alterations in immediate hypersensitivity-like reactions induced by a T cell-derived antigen-binding factor.

Previous studies have shown that T cell-dependent activation of mast cells to release serotonin is required for the elicitation of delayed-type hypersensitivity in mice. We have recently described an antigen-binding T cell factor that is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity. The T cell factor transfers the ability to elicit an antigen-specific immediate hypersensitivity-like ear-swelling reaction following local challenge with antigen. In the current study, alterations in the morphology of local tissue mast cells and vessels were studied by light and electron microscopy at the time of optimal swelling and increase in vascular permeability. Factor-induced reactions showed mild changes in metachromatic staining of mast cell granules compared with more profound changes that were found in reactions of antigen-challenged mice that were sensitized by intravenous injection with IgE antibody. Subtle changes in the ultrastructure of mast cells in reactions induced by the T cell factor included surface activation to form filopodial extensions, resulting in a significant increase in the surface density by stereologic analysis. The cytoplasm of these mast cells also showed signs of synthetic and metabolic activity with formation of vesicles and an increased prominence of the Golgi apparatus and mitochondria. Local vessels at sites of reactions due to the T cell factor or IgE showed intravascular accumulation of polymorphonuclear leukocytes, gaps at sites of endothelial cell junctions, and occasional emigration of the leukocytes into the perivascular area. This indicates that a vasoactive factor, such as serotonin, and chemotactic factors were released in both instances. However, in recipients of the T cell factor, this was accomplished with only moderate signs of overt mast cell degranulation and loss of granule density. Instead, there was formation of vesicles at the outer margin of the granules, in the perigranular membrane, and in the cytoplasm, accompanied by the surface activation. In contrast, mast cells from reactions in IgE-sensitized animals appeared to degranulate by a process of sequential compound exocytosis with no vesicle formation or cytoplasmic findings of increased synthetic or metabolic activity. The granules of these cells showed a great loss of density and many appeared swollen, resulting in overall swelling and increase in area of the cell.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Mechanisms of suppression in the transfer of contact sensitivity. Analysis of an I-J+ molecule required for Ly2 suppressor cell activity.

The passive transfer of contact sensitivity (CS) by immune cells can be inhibited with an antigen-specific T suppressor factor. This factor is composed of two subfactors: an antigen-specific subfactor made by an Ly1+ cell (PC1-F) and a antigen nonspecific subfactor made by an Ly2+ T cell (TNBSA-F). The suppressive activity of the complete factor can be eliminated by depleting the assay population of Ly2+ cells, even though it is the Ly1+ cell in the population that transfers the adoptive immunity. This suggests that the Ly2+ cell in the assay population is needed to transduce the suppressive signal to the Ly1+ effector cell of DTH. We found that an Ly2+ cell from immune animals could be induced to produce a cell free subfactor that overcame the requirement for this Ttrans cell in the suppression of CS by TsF. The induction required only PC1-F, TNP-coupled spleen cells, and resulted in the production of an antigen-nonspecific I-J+ subfactor by immune Ly2+, I-J+ cells. The need for the Ly2+ transducer cell could also be overcome by addition of an I-J+ molecule secreted by Ly1 T cells hyperimmunized to SRBC. A suppressor complex made from mixing the I-J+ molecule with TNBSA-F could directly suppress the functional activity of immune T cells not only to transfer CS, but also to deliver help to B cells in an in vitro PFC response. This suppressive complex is antigen-nonspecific and does not require Ly2+ T cells in the assay population for suppressive activity. These results indicate that effector factors of the suppressor circuit require two molecules; one that contains the functional suppressor material and one that serves as a "schlepper," a molecule needed to deliver the suppression to the appropriate target cell. The ability to construct a functional suppressor complex from two subfactors raised against different antigens, using different immunization procedures, which were isolated from factors exhibiting different functional activities suggests that certain cells of the immune system may play a universal role in "transducing" the suppressive signal.

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PubMed1983

Role of contrasuppression in the adoptive transfer of immunity.

The data presented in this paper show that the population of cells that adoptively transfer contact hypersensitivity are Lyt-1+ 2-, I-J- and nonadherent to V. villosa lectin. However, the adoptive transfer of immunity by this population of cells is successful only when the recipient has been treated in such a way as to impair the host immunosuppression mechanism. This population cannot, on its own, transfer immunity to adult, untreated naive recipients unless an additional population of immunoregulatory cells is present. This immunoregulatory population does not itself adoptively transfer immunity. This latter population is differentiated from the immune cells in that they are Lyt-1+ 2-, I-J+ and are adherent to V. villosa lectin. Both populations are required to adoptively transfer immunity to adult untreated naive recipients.

Animals↗

PubMed1983

T cells produce an antigen-binding factor with in vivo activity analogous to IgE antibody.

T cell-dependent activation of resident tissue mast cells is required for the elicitation of delayed-type hypersensitivity skin reactions in mice. A T cell-derived antigen-binding factor that transfers the ability to elicit an immediate hypersensitivity-like skin reaction is described and compared with a hybridoma IgE antibody. Both the T cell factor and IgE mediate reactions with increased vascular permeability and both are mast cell dependent, as they are inactive in two different types of mast cell deficient mice (W/Wv and Sl/Sld). The T cell factor was distinguished from IgE by affinity chromatography using specific anti-IgE and anti-factor antibodies and by a shorter duration of passive sensitization. The T cell factor is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity.

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PubMed1983

Ontogenic development of contrasuppression.

Using a xenogeneic graft-versus-host assay system, we have been able to document the sequential appearance of certain regulatory cells in newborn mice. Before birth, mouse spleen cells exhibit potent suppression that cannot be ameliorated by contrasuppressor cells. On the day of birth, the spleens contain equally potent suppressor cells, but these cells now can be inhibited totally by contrasuppressor cells. Between days 1 and 2 after birth, suppression, as picked up by our system, has disappeared. However, it can be found hiding behind contrasuppressor cells, as elimination of the latter cells with appropriate antisera reveals cells with the same suppressive potency as spleen cells taken 1 or 2 days earlier. Further, if the thymus is removed on the day of birth or 1 day later, the suppressor-obscuring cells do not appear. Thus, there appears to be an inherent ontogenic schedule that the thymus follows, which determines the time when different regulatory cells will emerge from it.

Aging↗

PubMed1983

Heterologous antisera to Lyt-1+, 2- -derived antigen-binding factor detect a subfactor of an antigen-specific suppressor factor and cell surface proteins on Lyt-1+, 2- and Lyt-1-, 2+ T cells.

Rabbits were immunized with TNP-specific Lyt-1+, 2- T cell-derived, antigen-binding proteins (PCI-F) released by T cells sensitized by skin painting with picrylchloride. The resulting antiserum (anti-PCI-F) bound to PCI-F and TNP-specific factors that suppressed delayed hypersensitivity (TSF) known to be comprised of PCI-F and Lyt-2+ -derived polypeptides released by cells sensitized by injection of trinitrobenzenesulfonic acid (TNBSF). Anti-PCI-F bound to T lymphocytes and 68,000 to 72,000 m.w. T cell surface proteins but not B cells on their surface proteins. Anti-PCI-F bound to both Lyt-1+ and Lyt-2+ T cells and surface proteins. A comparison of anti-PCI-F with anti-TSF indicates that anti-TSF contains specificity for Ly-2+ T cell-derived components of TSF and T cells not present in anti-PCI-F. The possibility of multiple isotypes of T cell receptors and antigen-binding molecules is discussed.

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