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Biomedical subjects

R J Scheper

Publications and source records attributed to R J Scheper.

At least 253 records · Page 14Linked to original sources
PubMed1987

Identification and quantitation of the expression of T cell surface markers during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig.

As there were discrepancies in previous data on the T cell nature of cells infiltrating the meninges at all stages of chronic relapsing experimental allergic encephalomyelitis (CREAE), experiments have been performed using a further monoclonal antibody (Mab) recognizing total T cell populations and the classic E rosetting technique. Cytospins were prepared of the meningeal inflammatory cells obtained by washing the brains of these animals, and stained by indirect immunoperoxidase. It was found that the T cell, as defined by both E rosetting and staining with the Mab CT5, is the major cell type found in the meninges during the development of CREAE. However, the staining with the Mab CT7, which recognizes a functionally relevant antigen, showed that there is a discrepancy between the numbers of lymphocytes stained compared to the results with CT5 and E rosettes. Furthermore, the antigen recognized by CT7 appeared to be modulated during the disease. The possible functional relevance and its relation to clinical remission and relapse are discussed.

Animals↗
PubMed1987

Changes in lymphocyte subsets after treatment with cyclophosphamide and during the development of contact sensitivity in the guinea pig.

Changes in lymphocyte subpopulations were investigated in guinea pig lymph nodes during the development of contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) and following the injection of cyclophosphamide (CY; 300 mg/kg) using a panel of monoclonal antibodies against guinea pig lymphocyte surface markers. Application of a sensitizing dose of DNFB to the ear resulted in a significant increase in the number of cells recovered from the draining auricular and cervical lymph nodes, 4 and 6 days post sensitization. A significant increase in the number of cells in the contralateral cervical node was found at day 6 but not at day 4. At 4 days postsensitization the proportions of Ia positive lymphocytes were higher than those of immunoglobulin positive B cells in the draining auricular and cervical node and the contralateral cervical lymph nodes suggesting T-cell "activation". Four and six days after sensitization there were no significant changes in the proportions of Pan T and T suppressor/cytotoxic (Ts/c) positive lymphocytes in the draining auricular and cervical lymph nodes. Although contact sensitivity is "classically" a T-cell mediated phenomenon there was a significant increase in the proportion of B cells found in the draining auricular node 4 days after sensitization as compared to the "normal" auricular node. 1, 2, 3 and 7 days after injection of CY there was a significant depletion in the proportion of B-lymphocytes in the cervical lymph node. This effect was maximal between 2 and 3 days after CY and was paralleled by an increase in the proportion of Pan T positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Local and systemic desensitization induced by repeated epicutaneous hapten application.

Frequent skin exposure of guinea pigs to the contact sensitizing agents dinitrochlorobenzene or 4-ethoxymethylene-2-phenyloxazolone induced both systemic hyposensitization and local unresponsiveness within 8 weeks. Both phenomena were hapten-specific. Decreased systemic reactivity in repeatedly painted guinea pigs is probably not due to receptor blockade or the development of hapten-specific antibodies, but rather to transient sequestration of hapten-specific effector cells within lymph nodes draining the site of hapten exposure. After discontinuation of allergen exposure, effector cells return into the circulation, as indicated by a reversal of systemic hyporesponsiveness within 5 weeks. The persistence of a cellular infiltrate at the site of repeated application and the hapten-specific unresponsiveness at this site suggest that suppressor cells play a role in local unresponsiveness. Upon discontinuation of allergen exposure, local unresponsiveness rapidly dissolves (within one week). Since the circulation is still depleted of effector cells, residual hyporesponsiveness may persist for longer periods.

Administration, Topical↗
PubMed1987

In vitro studies in nickel allergy: diagnostic value of a dual parameter analysis.

A comparison was made between the diagnostic value of assaying nickel-induced lymphocyte proliferation (lymphocyte transformation test, LTT) and migration inhibition factor (MIF) production in nickel contact sensitivity. Although lymphocyte proliferation was significantly increased in the group of patients with skin test reactivity to nickel, positive LTT were also frequently found in skin test-negative subjects: in 63% of subjects with and in 30% of subjects without a history of metal allergy. This would limit the value of the LTT as an in vitro correlate of skin test reactivity. However, in certain patients positive lymphocyte transformation may reveal nickel sensitization at a time of undetectable skin reactivity. Data obtained with the macrophage migration inhibition test (MMIT) showed a good correlation with nickel patch test reactions. Accurate determination of MIF became feasible by using cells from the human monocytoid cell line U937 as target cells in a microdroplet agarose assay. Using this MMIT, positive reactions occurred in 13% of the healthy controls and false-negative reactions were found in 26% of patients with positive skin test reactivity to nickel. As LTT and MMIT data appeared to be only weakly correlated in the individuals tested, a dual parameter analysis was performed. An excellent correlation [p = 1.8 (10(-8]] was found between skin test and in vitro reactivity for individuals with matching in vitro results (60% of all individuals tested). In those individuals with discordant in vitro data, skin testing will remain indispensable for diagnosing nickel allergy.

Cell Line↗
PubMed1987

Effect of P15E related retroviral material isolated from head and neck carcinomas on delayed type hypersensitivity skin reactions in mice.

Low molecular weight factors, derived from head and neck carcinomas (H/N ca LMWFs), exert a serious inhibitory effect on monocyte chemotaxis both in vivo and in vitro. This effect can be neutralized by the treatment of the factors with three different monoclonal antibodies to P15E, one of the structural envelope proteins of murine leukemia virus (MuLV). In this study, we report the effect of the H/N ca LMWFs on the delayed type hypersensitivity responsiveness in mice: the factors significantly inhibited the 24 hour DNFB skin reaction. These effects of the H/N ca LMWFs were again neutralizable by antibodies to P15E. Additional experiments showed that the H/N ca LMWFs had equal suppressive effects on toxic skin reactions to croton oil, and this indicates that the P15E-like H/N ca LMWFs exert their effect by aspecific mechanisms.

Aged↗
PubMed1987

Immunotherapeutic effects of local chemotherapy with an active metabolite of cyclophosphamide.

A new approach is described for the use of cytostatic drugs as biological response modifiers (BRM's). Under restricted conditions, strong potentiation of T-effector function can be obtained through preferential elimination of suppressor cells. Recent studies from our group have demonstrated that such conditions are fulfilled when low dosages of certain drugs are injected at a site of low antigenic stimulation. Furthermore, local injection of cytostatic drugs not only enhances the development of cell-mediated immunity in non-sensitized animals, but also facilitates the reversal of existing immunological tolerance. These data shed new light on the tumor regression and induction of tumor immunity observed upon intralesional chemotherapy in experimental tumor models.

Adjuvants, Immunologic↗
PubMed1986

Human lymphocyte-high endothelial venule interaction: organ-selective binding of T and B lymphocyte populations to high endothelium.

We wished to determine whether human lymphocytes, like their murine counterparts, show organ-specific interactions with high endothelial venules (HEV). Functional HEV-binding ability was measured by an in vitro assay of lymphocyte adherence to HEV in frozen sections of human lymphoid tissues which was adapted from rodent systems. It was found that human lymphocytes bind selectively to HEV and that, whereas mature T lymphocytes bind preferentially to HEV in peripheral lymph nodes and tonsils, B lymphocytes show preferential binding to HEV in GALT. Moreover, by analyzing the binding characteristics of T4+ and T8+ T cell populations, it was found that T8+ cells adhere preferentially to HEV in GALT and mesenteric lymph nodes and tonsil, and that T4+ cells bind slightly better to HEV in peripheral lymph nodes. The above findings indicate that organ--specific lymphocyte-endothelial cell recognition mechanisms exist also in humans, and suggest that these mechanisms play an important role in normal and pathologic lymphocyte traffic.

B-Lymphocytes↗
PubMed1986

Defective monocyte chemotaxis in patients with head and neck cancer. Restoration after treatment.

Monocyte chemotactic responsiveness (MCR), as measured by the monocytes' capacity to migrate through polymer (Millipore) membranes toward the chemoattractant casein, is impaired in all patients with head and neck cancer thus far examined. Using a more rapid and sensitive test system, the polarization assay, we tested the MCR in 24 patients with head and neck cancer and 31 controls and compared it with the outcomes of the well-established Boyden chamber method. The results of both methods correlated well. All patients showed a seriously depressed monocyte chemotaxis before treatment when tested in the polarization assay. Nine patients were reexamined after surgery, and in seven patients the defective MCR was restored. This illustrates that tumor-derived factors are probably responsible for the inhibitory effect on monocyte chemotaxis. The polarization assay has the potential for predicting early relapse.

Adult↗
PubMed1986

Immunosuppressive retroviral P15E-related factors in head and neck carcinomas.

We report on the effect of low molecular weight factors (LMWFs) derived from 14 different head and neck carcinomas on the chemotactic responsiveness of healthy donor monocytes, as measured by their polarization activity. The factors inhibited the polarization of the monocytes significantly (61.5% to 94.5% vs 12.5% to 29% in cases where the LMWF was derived from healthy oral mucosa). The inhibitory effect exerted by these LMWFs could be neutralized only by absorption with one of three different murine monoclonal antibodies or a rabbit polyclonal antibody to the murine retroviral envelope protein P15E. This shows that retroviral-related material is present in head and neck carcinomas and that this material is responsible for the observed defective polarization that probably underlies the earlier described defects on monocyte chemotactic responsiveness.

Antibodies, Monoclonal↗
PubMed1986

Immunocytochemical identification and quantitation of mononuclear cells in the meninges during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig.

To investigate the role of mononuclear cells in the meninges at all stages of chronic relapsing experimental allergic encephalomyelitis, juvenile guinea pigs were inoculated with isogeneic spinal cord in Freund's complete adjuvant (FCA) in parallel with animals inoculated with FCA alone as age-matched controls. Cytospins were prepared of the meningeal inflammatory cells obtained by washing the brains of these animals. These cytospins were stained by indirect immunoperoxidase, using a panel of monoclonal antibodies (Mabs) recognizing "activated" macrophages (M phi s), Ia antigen, total T cells and a putatively T-cell-suppressor subset, and an antiserum against immunoglobulins. The inflammatory response was quantitated and the proportions of the different cell types were determined. It was found that the total number of infiltrating cells correlated with the neurological symptoms of the disease. "Activated" M phi s increased significantly during the disease, in line with clinical signs. The expression of the Ia antigen, found on both lymphocytes and M phi s, also appeared to correlate with the disease. There was no increase in putative T-suppressor-cells during remission but there was a significant rise in the proportion of both cells staining with anti-immunoglobulins and plasma cells during relapse.

Animals↗
PubMed1986

Intradermal administration of 4-hydroperoxy-cyclophosphamide during contact sensitization potentiates effector T cell responsiveness in draining lymph nodes.

4-Hydroperoxy-cyclophosphamide (4-HPCY) is an in vitro active form of cyclophosphamide. In a previous study, using an in vivo contact sensitivity model in the guinea pig, we demonstrated that intradermal injection of small amounts (50-200 micrograms) of 4-HPCY at the sensitization site resulted in strong potentiation of contact hypersensitivity (Boerrigter and Scheper, 1984). It was postulated that 4-HPCY induces a local decrease of feedback control within the draining antigenically stimulated lymph nodes. The present data are in support of this view: Lymph node hyperplasia induced by contact sensitization (to dinitrochlorobenzene or oxazolone) was further enhanced by 4-HPCY treatment. The paracortical area was preferentially enlarged. 4-HPCY-treated lymph nodes showed an augmentation of hapten-specific T effector cell function as determined in transfer experiments. The response of such lymph node-derived cells to the T cell mitogen PHA was enhanced. Although 4-HPCY treatment resulted simultaneously in a decrease in responsiveness of draining lymph node-derived cells to the B cell mitogen lipopolysaccharide, anti-hapten antibody production was not affected. The present study demonstrates that important similarities exist between the effects of local 4-HPCY treatment and systemic cyclophosphamide pretreatment on the immune response. As systemic treatment with a high dose of cyclophosphamide is known to have serious side effects, the present local protocol provides a new attractive and versatile strategy for T cell immunopotentiation.

Animals↗
PubMed1986

Local administration of various cytostatic drugs after subcutaneous immunization enhances delayed-type hypersensitivity reaction to sheep red blood cells in mice.

Delayed hypersensitivity reaction in mice was enhanced with various anti-cancer drugs administered at the site of antigenic stimulation during 4 days following sensitization. The immunopotentiating effect of the presented local chemotherapy protocol is thought to result from impairment of a regulatory circuit, with activated suppressor T cells (Ts) as target rather than Ts precursors or Ts-inducing antigen-presenting cells.

Animals↗
PubMed1986

Hand eczema in hairdressers and nurses: a prospective study. I. Evaluation of atopy and nickel hypersensitivity at the start of apprenticeship.

A prospective study of the development of hand eczema was initiated in 86 junior hairdressers and 217 junior nurses. Data obtained at the start of their apprenticeships are presented. None of the junior apprentices presented with hand eczema, but a history of hand eczema was reported by 22/303 (7%) of the students. Almost half of this group (10/22, 45%) could be classified as atopics. Students without a history of hand eczema showed a similar frequency of atopy (17%) as observed in the general population. History of hand eczema was not related to nickel hypersensitivity, as assessed by patch testing. The incidence of nickel hypersensitivity was high in junior hairdressers (26%), compared to junior nurses (12%). Information as to previous contacts with nickel suggested that development of nickel allergy had been promoted by ear-piercing. A lower incidence of nickel hypersensitivity was observed if this potentially sensitizing event had been proceeded by orthodontic treatment with nickel-containing materials. This phenomenon is discussed in terms of orally-induced tolerance.

Adolescent↗
PubMed1986

Specific plasma cell accumulation in antigen-induced chronic inflammation in the guinea pig peritoneal cavity.

Specificity of plasmacellular infiltration was studied using a guinea pig peritoneal inflammation model. Acute and chronic inflammations were induced by repeated injections of either of two non-crossreacting antigens (DNP-BSA and PPD). With an enzyme-immunohistochemical sandwich procedure allowing quantitation of DNP-BSA-specific plasma cells, specificity of plasmacellular infiltration could be demonstrated. DNP-BSA-specific antibody-forming cells were found not to enter inflammatory reactions elicited by PPD. Our data support the hypothesis that virtually all plasma cells in a chronic inflammatory exudate release antibodies specific for antigens that are locally available, and that such antigens are likely to play a central role in the perpetuation of chronicity.

Animals↗
PubMed1985

Production of monoclonal antibodies defining guinea pig T-cell surface markers and a strain 13 Ia-like antigen: the value of immunohistological screening.

The production and characterization of eight monoclonal antibodies (MAbs) against surface markers of guinea pig T-cells is reported. MAbs CT5 and CT7 define putative pan-T-cell markers. CT5, however, also reacts with the B-cell leukemic line L2C. MAb CT6 is reactive with less than 30% of peripheral T-cells. MAbs CT1, 2, 3, 4, and 8 are reactive with lymphocytes, but not with germinal center B-cells. In addition to the CT's, a MAb (CI-13.1) has been prepared that reacts with an Ia-like antigen on cells of strain 13 and outbred guinea pigs, but not with cells of strain 2 animals. CI-13.1 cross-reacts with human tissue sections: About 30% of the OKIa-positive dendritic cells in the human dermis are recognized by CI-13.1. In the course of production and characterization, various binding assays and an immunohistological method were used for determining the antibody specificity. Immunohistological screening was found to be the most informative method.

Animals↗
PubMed1985

Hapten-specific T-cell lines in guinea-pig contact sensitivity: carrier specificity and specific accumulation.

Dinitrophenyl-specific T-cell lines were established by culturing lymph node-derived lymphocytes from dinitrochlorobenzene-sensitized guinea-pigs with dinitrophenyl-modified macrophages. Cells from this line were all Ia-positive and formed E-rosettes with rabbit erythrocytes; no Ig-positive cells were present in this suspension. Expanded cells exhibited enhanced in vitro and in vivo activity as demonstrated by DNA synthesis and systemic adoptive transfer of contact sensitivity. In vitro DNA synthesis was elicited not only be specific hapten-modified macrophages but also by conjugates of the hapten with homologous (GPA) and even heterologous (BGG, HSA) proteins, thus demonstrating the loss of carrier specificity. Moreover, the proliferative response of expanded cells was elicited not only with hapten-modified syngeneic (strain 2) but also with allogeneic (strain 13) macrophages. Cells from hapten-modified T-cell lines, but not from lymph nodes from in vivo primed guinea-pigs, showed specific accumulation in contact sensitivity skin test sites. Attempts to establish hapten-specific T-cell clones were also at least partially successful.

Animals↗
PubMed1985

Penicillin allergy and the relevance of epicutaneous tests.

Epicutaneous tests with penicillins are important in the evaluation of penicillin allergy in patients who have shown a delayed urticarial or maculo-papular rash after the administration of penicillin derivatives. Of 23 patients who showed positive epicutaneous tests only 5 also showed immediate-type reactivity upon subsequent intracutaneous tests with the major determinant of penicillin. Moreover, patients with positive epicutaneous tests were evidently immunologically reactive on penicillins, since lymphocytes from 14 out of 17 patients showed increased DNA synthesis induced by penicillin G and ampicillin in vitro. The performance of epicutaneous tests with various penicillin derivatives is recommended as a first step in establishing penicillin allergy, because it is a safe method and because an extra group of sensitized patients is detected.

Ampicillin↗