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Biomedical subjects

R J Scheper

Publications and source records attributed to R J Scheper.

At least 271 records · Page 15Linked to original sources
PubMed1984

Evaluation of various cytostatic drugs as local immunotherapeutic agents.

The cytostatic drugs methotrexate, 5-fluorouracil, adriamycin, vincristin, cisplatinum, VP-16 and the newly synthesized, stabile cyclophosphamide-derivative Z-7557, were screened for possible immunopotentiating effects in local chemotherapy. With an in vivo contact sensitivity model in guinea pigs, low dosages of the drugs were introduced into antigenically stimulated lymph nodes by intradermal injections following sensitization. Marked till strong potentiation of T-cell function, as measured by the development of contact hypersensitivity, was observed with all drugs tested, except for methotrexate and 5-fluorouracil. With a similar local chemotherapeutic protocol in the guinea pig line 10 hepatocellular carcinoma-model, these latter drugs have been reported earlier to be exceptional in failing to induce tumor regression and tumor immunity. Our present results suggest that local chemotherapy of malignancies not only may reduce local tumor load, but also may affect distant metastases by facilitating the development of tumor-specific immunity.

Adjuvants, Immunologic↗
PubMed1984

Induction of contact sensitivity to a broad variety of allergens with haptenized macrophages.

Using guinea pigs an analysis could be made of various aspects of contact sensitivity (CS) induced by subcutaneous injection of syngeneic haptenized macrophages (oil-induced peritoneal exudate cells, PEC) as compared to epicutaneous sensitization. Very little PEC-bound hapten (dinitrochlorobenzene, or oxazolone) is needed for optimum sensitization. Nevertheless, both sensitization methods induce a state of CS that may last for over 6 months, give rise to hapten-specific antibodies with a similar isotype distribution, and show susceptibility to cyclophosphamide pretreatment. In addition, time courses and microscopic appearance of skin test reactions after either way of sensitization are identical. CS to a broad variety of physicochemically different antigens, including nickel, penicillin, and acrylates, is readily induced by syngeneic PEC, haptenized following a standardized procedure. As Freund's complete adjuvant is known to cause serious side effects like ulceration and long-lasting granuloma formation, immunization with haptenized PEC should now be considered as a clean and effective alternative in experimental CS studies.

Allergens↗
PubMed1984

Induction of immunological tolerance by oral administration of nickel and chromium.

Oral administration of nickel-chromium to guinea pigs by way of a fixed occlusal splint, or the incorporation of metallic powder or salts into the pelleted food, did not induce hypersensitivity to these metals. In addition, a subsequent attempt to immunize the pre-treated guinea pigs failed in most animals, whereas non-pre-treated guinea pigs became clearly hypersensitive. These results show that oral administration of nickel and chromium induced a state of (partial) tolerance to both metals.

Administration, Oral↗
PubMed1984

Local administration of cytostatic drug 4-hydroperoxy-cyclophosphamide (4-HPCY) facilitates cell-mediated immune reactions.

4-Hydroperoxy-cyclophosphamide (4-HPCY) is a cyclophosphamide (CY) derivative that, unlike CY, does not need liver conversion for its action. This new drug has been recently described to preferentially eliminate suppressor B and T lymphocytes in vitro in both mice and man. Using an in vivo contact sensitivity model in the guinea-pig, we introduced 4-HPCY into antigenically stimulated lymph nodes by local intradermal injection following sensitization. Strong potentiation of contact sensitization was achieved by local administration of doses higher than 50 micrograms 4-HPCY daily on 4 days subsequent to sensitization. Contact hypersensitivity was found to be enhanced for at least 6 weeks. In addition it could be demonstrated that local administration of 4-HPCY not only enhanced the development of delayed hypersensitivity in normal animals, but also facilitated the reversal of previously induced immunological tolerance. The applicability of this new strategy for potentiation of effector T cell function, especially with respect to the treatment of malignancies, is stressed.

Adjuvants, Immunologic↗
PubMed1983

Direct measurement of in vitro antibody production using an enzyme-linked immunosorbent assay.

A rapid and sensitive enzyme-linked immunoassay is described for quantitation of the secretion of cellular products during short-term (1-20 h) culture in vitro. The method is based on culture of cells, serially diluted in antigen or antibody-coated polystyrene microtitre wells. The wide applicability of this method for measurement of anti-hapten antibody, immunoglobulin and lymphokine production is stressed.

Animals↗
PubMed1983

Allergic reactions, "spillover' reactions, and T-cell subsets.

A strong positive, allergic patch-test reaction was elicited in 15 patients with an established allergy for a particular allergen. Patches with a marginally irritating concentration of sodium lauryl sulfate (SLS) were applied at fixed distances. The SLS patch situated adjacent to the allergic reaction was significantly enhanced in 12 of 15 patients (P less than 0.01) compared to more distant SLS reactions ("spillover'). Only quantitative differences were observed in the histologic pictures of the different types of reaction. The infiltrate consisted of lymphocytes and histiocytes, mainly located perivascular in the upper dermis. T-cell subsets were assessed with monoclonal antibodies using an immunoperoxidase technique. The distribution of the different T cells was the same for both reaction types. T cells located outside the perivascular infiltrates (e.g., in the epidermal vesicles) were OKT-8-positive (cytotoxic/suppressor T lymphocytes). Immunofluorescence examination did not show different patterns for the allergic or "enhanced toxic' reactions with regard to the presence of immunoglobulins and complement. The "spillover' phenomenon may cause false-positive patch-test reactions.

Adult↗
PubMed1983

Angry back or the excited skin syndrome. A prospective study.

Allergens eliciting weak positive reactions were retested to ascertain their reproducibility. Weak positive patch test reactions, concomitant to other weak or strong positive reactions, were retested after 3 weeks in 61 patients. 79 reactions were retested; 35 (44.3%) were negative. Allergens which are marginal irritants, e.g., formaldehyde, often gave weak positive reactions which were lost at retesting. In patients without dermatitis but with several strong positive reactions, lost reactions were frequently encountered, suggesting that strong reactions induced a state of hyperirritability. False positive reactions were often found in the proximity of strong reactions. We attempted to develop a nonspecific irritant (sodium lauryl sulfate) as a hyperirritability marker. A correlation between the score of this test and false positive reactions was not found. It is concluded that weak positive reactions should not be accepted as a proof of sensitization. The allergens eliciting these reactions should be retested at a later date.

Adolescent↗
PubMed1983

Antigen-specific T-cell lines in DNCB-contact sensitivity in guinea pigs.

Expanded DNP-specific guinea pig T cells exhibit enhanced in vitro and in vivo activity as demonstrated by DNA synthesis and systemic adoptive transfer of contact sensitivity. Moreover, expanded lymphocytes are capable of accomplishing local passive transfer of contact sensitivity and producing interleukin 2, vascular permeability-increasing and macrophage migration-inhibiting factors. Expansion of hapten-specific lymphocytes offers a suitable model for studying eliciting mechanism of allergic contact dermatitis in humans.

Animals↗
PubMed1983

Depression or enhancement of skin reactivity by inflammatory processes in the guinea pig.

An animal model for the excited skin syndrome was developed in the guinea pig. Hyperirritability of the skin could be induced by immunization with Freund's complete adjuvant (FCA). This hyperirritability was evident from the enhancement of both patch test reactions to an irritant (sodium lauryl sulfate) and open epicutaneous test reactions to a contact sensitizer (2,4-dinitrochlorobenzene). The skin tests were performed at sites other than those pretreated with FCA. Maximum enhancement was observed in a period 3-5 weeks after FCA immunization. A similar but less marked hyperirritability could be induced by eliciting a localized chronic croton oil dermatitis. The period of hyperirritability induced by FCA or croton oil was preceded by a short period (1-14 days) of depressed skin reactivity.

Acute Disease↗
PubMed1983

Comparative migration of T- and B-lymphocyte subpopulations into skin inflammatory sites.

Homing of 51Cr-labelled spleen and lymph node-derived T- and B-cell subpopulations into inflammatory sites in the skin, as well as into lymphoid and non-lymphoid organs, was studied in outbred and inbred guinea-pigs. The early progeny of activated T cells were demonstrated in immunologically-mediated inflammation of the skin, for example a cell-mediated immune reaction and a reversed passive Arthus reaction. In contrast, spleen and lymph node-derived B cells were virtually unable to enter inflammatory sites. Organ-specific homing of T and B cells was detected. The significance of these observations for the interpretation of results of lymphoid cell transfers in guinea-pigs is discussed.

Animals↗
PubMed1983

Induction of immunological memory in the skin. Role of local T cell retention.

Using an experimental contact sensitivity model in guinea-pigs, evidence is presented that hapten (DNCB or oxazolone) specific T lymphocytes may persist for several months in previous sites of inflammation. Immunological memory, revealed by accelerated contact skin reactions upon retesting with the hapten, was limited to the original contact skin reaction sites. This 'local skin memory' to DNCB or oxazolone could be induced in both specific and non-specific skin inflammatory reactions, provided the animals had been sensitized to the hapten not longer than 2 weeks before. In animals which had been sensitized more than 1 month earlier, local skin memory could be induced if the animals received a booster application of hapten shortly (0-2 days) before primary skin testing. From these results we conclude that recently activated T cells may enter inflammatory sites non-specifically, producing specific local immunological memory. This memory may last several months. Accumulation of hapten specific T cells at inflammatory sites may be important in retest reactivity, in flare-up reactivity and in chronic inflammation.

Animals↗
PubMed1982

Delayed time course of irritation by sodium lauryl sulfate: observations on threshold reactions.

Irritant reactions to sodium lauryl sulfate were induced on the backs of 20 volunteers by means of patch test occlusion for 24 h. Different concentrations ranging from 0.25% to 2% were used, the lowest concentration being borderline irritant. The skin tests were read at 24, 48 and 72 h. Both the % of responding individuals and the intensity of the skin reactions were maximal at 48 h for all test concentrations. It is concluded that irritants may provoke inflammatory reactions which are not completely developed after 24 h, and are thus very similar to allergic patch test reactions.

Adult↗
PubMed1982

Demonstration of accelerated and increased migration inhibition factor release in vivo in a PPD retest reaction.

Sites at which positive skin-test reactions have been elicited exhibit an accelerated (so-called 'retest') reaction upon local reinjection of the antigen used for primary skin testing. When using a peritoneal cavity inflammation model in guinea pigs, local migration inhibition factor (MIF) release in vivo was studied in both primary and retest reactions to purified protein derivative. Increased retest reactivity could be demonstrated to coincide with an instantaneous and intense local MIF release. Estimation of both the absolute number of the antigen specificity of lymphocytes present in the peritoneal cavity at the time of retesting (170 h after primary testing) showed that the early burst of MIF release is primarily due to nonspecific local retention of increased numbers of lymphocytes.

Animals↗
PubMed1982

Differential capacity of macrophages from various sources to act as hapten-specific stimulator cells in vitro.

Lymphocytes from 2,4-dinitrochlorobenzene, contact sensitized guinea pigs show increased DNA synthesis in vitro when stimulated by dinitrophenylated macrophages. In this study, macrophage-containing cell suspensions were isolated from various sources (spleen, lungs, peritoneal cavity) and from the peritoneal cavity also after different stimuli (oil, thioglycollate, starch, lymphokines). These cells were then haptenized and investigated on their capacity to act as stimulator cells in vitro. In addition, a possible relationship between Ia-positivity of the hapten-presenting cell suspensions and the induction of DNA synthesis was studied. The results demonstrate (1) that the hapten-presenting capacity of macrophages differs with respect to the source and the way of elicitation, (2) that oil-induced peritoneal exudate cells are the most suitable stimulator cells for in vitro assays in contact sensitivity, and (3) that the cellular expression of Ia antigens is in itself no warrant for hapten-presenting capacity.

Animals↗
PubMed1981

Restrictions to the use of 111 indium-oxine as a radiolabel in lymphocyte migration studies.

Guinea pig T lymphocytes were labelled with various concentrations of 111In-oxine. The capacity of these cells to migrate into a skin inflammatory site was compared with that of 51Cr-labelled cells. The results show that even with low dosages of 111In-oxine which did not impair lymph node localization (1-10 microCi/10(8) cells/ml), migration into an inflammatory site was markedly reduced. Moreover, using this isotope, a significant contribution to the radioactivity recovered from an inflammatory site is made by the local accumulation of non-cell-bound label. These results stress the limited use of 111 In-oxine as a radiolabel in lymphocyte migration studies.

Animals↗
PubMed1981

In vitro DNA synthesis in lymphocytes from guinea pigs epicutaneously sensitized with DNCB.

Lymph node lymphocytes from guinea pigs sensitized with the hapten homogenized in Freund's complete adjuvant or pretreated with cyclophosphamide shortly before an epicutaneous sensitization are capable of responding in vitro to a larger set of antigenic preparations than the lymphocytes from only epicutaneously sensitized animals. This may be due to a formation of a larger set of antigenic determinants when the hapten was homogenized in Freund's complete adjuvant or to a formation of a larger repertoire of lymphocytes capable of recognizing these determinants as it might be the result of pretreatment with cyclophosphamide. These procedures may also change the proportion of responding cells in the lymphocyte suspensions.

Animals↗
PubMed1981

Characterization of lymphocyte subpopulations which exhibit enhanced DNA synthesis in vitro in DNFB contact sensitive guinea-pigs.

Different lymphocyte subpopulations were prepared from lymph nodes and spleen obtained from 2.4-dinitrofluorobenzene/Freund's complete adjuvant (DNFB/FCA) sensitized guinea-pigs. The capacity to react in vitro to secondary antigenic (dinitrophenyl-modified syngeneic macrophages, DNP-MO) stimulation by an increased DNA synthesis, appeared to be restricted to those T cells which lack receptors for IgG-Fc (T gamma -). We confirmed the existence in this species of an IgG-Fc receptor-positive T-cell subset, which is particularly represented in the spleen (up to 56%). These T gamma + cells apparently are not of monocyte lineage as they show strong PHA-responsiveness and a lack of non-specific esterase staining, whereas the majority of these cells form RRBC-rosettes. Neither B nor T gamma + cells appeared to act as suppressor cells in the secondary DNP-MO-driven proliferative response.

Animals↗