摘要:

AbstractMononuclear cells (MNC) from normal humans consistently failed to give nonspecific cytotoxic responses. However, after removal of T cells by sheep erythrocyte (E) rosetting, the remaining non‐RFC (rosette‐forming cells) now gave significant nonspecific cytotoxic responses against both autologous and allogeneic target cells. Reconstitution experiments with T cell subpopulations failed to suppress these nonspecific non‐E ‐RFC‐mediated cytotoxic responses. There was also no evidence to indicate the involvement of antibody in this nonspecific cytotoxicity. The cytotoxic cells were characterized as non‐E ‐rosetting, non‐phagocytic, and glass adherent lymphocytes; no evidence of monocyte‐macrophage participation was found.The inductive trigger of non‐E ‐RFC‐mediated cytotoxicity was found to be soluble factors released by T cells during E‐rosette formation at 4°C. Incubation of MNC with horse, marmoset and human erythrocytes under identical conditions failed to trigger cytotoxicity. The incubation of quiescent MNC with E‐rosetting supernatants (ERS) induced nonspecific cytotoxic responses equivalent to those mediated by separated non‐E ‐RFC. ERS‐activated MNC destroyed both autologous and allogeneic target cells. The ERS supernatants themselves were not cytolytic. These findings suggested that cell separation procedures, and possiblyin vivoevents, which activate T cells may also induce non‐T ce

ISSN:0014-2980    

DOI:10.1002/eji.1830070202

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractThe previously demonstrated role of H‐2 gene products in nonimmune cell interactions was further analyzed. As model of such interactions served the erythropoietic performance (in terms of59Fe uptake) of bone marrow cell (BMC) inocula in the cellular environment of the spleen of massively irradiated hosts. When the performance in syngeneic hosts is taken as standard, the performance of cells from the same pool in H‐2 disparate (congenic) hosts is subnormal. The inhibition was also observed in two congenic strain combinations where the H‐2 disparity did not involve the I region. The capacity of BMC to distinguish H‐2 ‐identical and H‐2 ‐disparate hosts could be greatly reduced or virtually abolished by enzymatic digestion of certain cell surface carbohydrates. An essential effect of neuraminidase was further increased by emulsin. When the digested cells were left for 6 h in an enzyme‐free medium, their capacity to dinstinguish H‐2 disparities recovered. A pretreatment with papain, which cleaves a large fragment of the H‐2 protein carrying both the antigenic site and the carbohydrate chain, had an effect comparable with but no greater than the sugar‐removing enzymes. The enzymatic effect was largely due to the impairment of the performance of BMC in H‐2 ‐identical hosts rather than to an improvement in H‐2 ‐disparate ones. The neuraminidase‐ and emulsin‐sensitive groupings thus seem to be essential for the cells to recognize “self” rather than “non‐self” and to interact with H‐2 ‐identical cells in physiological processes. A hypothesis is proposed that in H‐2 glycoproteins, the antigenically and physiologically active sites are distinct, being located in the protein and carbohydrate parts of the molecules, respectively. It is further suggested that the normal function of the H‐2 products might consist in providing the cell surface with structures which are complementary to similar structures on other cells; the carbohydrate moiety seems to be essential for this type of physiological interaction in contrast to the key and lock‐type of complementarity in imm

ISSN:0014-2980    

DOI:10.1002/eji.1830070203

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractA radioimmunoassay was developed for the phagocytosis‐stimulating peptide tuftsin, H‐Thr‐Lys‐Pro‐Arg‐OH, and preliminary results of its use in evaluating tuftsin levels in human blood are presented.Synthetic tuftsin was rendered antigenic through coupling of p‐diazonium phenylacetyl‐tuftsin to bovine serum albumin (BSA). Using the BSA‐tuftsin conjugate to immunize rabbits, antisera were obtained that bound125I‐labeled p‐aminophenylacetyl‐tuftsin at dilutions up to 1:1500 (maximal binding 25–3 0 %). Binding of the radiolabeled peptide was inhibited by tuftsin and some of its synthetic N‐terminal analogs but was not affected by various unrelated natural and synthetic peptides. The amino acid sequence Lys‐Pro‐Arg‐OH appears to be the antigenic determinant recognized by the rabbit antibodies.Using the radioimmunoassay, quantitative determination of material immuno‐chemically related to tuftsin was performed in the sera of intact and splenectomized subjects after treatment of the sera with trypsin. Sera from normal patients (21 cases) were found to contain an average ± standard error of 278.47 ± 13.49 ng/ml, whereas those of patients who underwent traumatic (5 cases) and elective (6 cases) splenectomy contained 239.0 ± 47.68 ng/ml and 94.71 ± 22.5 ng/ml, respectively. No correlation was found between levels of IgG in serum and that of tuftsin‐like material.Analysis of purified IgG fragments, Fab from man and from rabbit and Fc from rabbit, clearly demonstrated that tuftsin is located or bound to the latter polypeptide. It was, of course, also found to be prese

ISSN:0014-2980    

DOI:10.1002/eji.1830070204

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractLow zone tolerance (LZT) to bacteriophage fd seems to be a type of tolerance which is primarily caused by suppressor T cells. The aim of this paper is to analyze their mode of action. For the induction of antigen‐specific suppressor cells in hydrocortisone pre treated CBA mice, we use tolerogenic and immunogenic doses of antigen. Suppressor activity can be demonstrated upon transfer of spleen cells into normal syngeneic mice. After immunization these animals are unable to produce IgG antibody against phage fd, whereas the IgM response is not suppressed. The half‐life of transferred suppressor cells in nonimmunized animals is 5–6 weeks. The target of suppression are unprimed T helper cells, whereas primed helper cells cannot be blocked. T helper cells become ‘resistant’ to suppression 18–3 6 h after contact with antigen. Differentiation from unprimed B into B memory cells is unaffected, yet under suppression conditions persisting B memory cells are blocked in IgG production. The experimental data are incorporated into a m

ISSN:0014-2980    

DOI:10.1002/eji.1830070205

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractXeno‐sensitization of human peripheral blood lymphocytes (PBL) against mouse lymphoid cells has been studiedin vivoin a local graft‐vs. ‐host (GVH) assay andin vitroin a mixed lymphocyte culture‐cell‐mediated lympholysis system. Human PBL were injected into the footpads of mice rendered unresponsive by total‐body irradiation, and these were subsequently tested for the presence of cytotoxic cells in the draining popliteal lymph node (LN). In spite of a definite PBL‐induced LN proliferation, no cytotoxic activity was detected against mouse target cells. In contrast with the GVH assay, human PBL collected after 7 days ofin vitroculture in the presence of irradiated mouse cells, were strongly cytotoxic against mouse target cells. The antigenic specificities recognized byin vitroeducated cells were primarily those coded for by the H‐2 complex. Only target cells with an H‐2 haplotype identical to that of the sensitizing mouse strain or with at least an H‐2 D end in common with that strain were killed by xeno‐sensitized lymphocytes. Mouse target cells derived from congenic resistant strains remained unaffected. It was verified thatin vitroeducated PBL depleted of B cells retained their cytotoxic effect, indicating that non‐B cells and probably T cells were i

ISSN:0014-2980    

DOI:10.1002/eji.1830070206

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractThe structure of the terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10(GAT) has been investigated. GAT appears very heterogeneous in size as determined by gel filtration on a Sephadex G‐1 00 column. A dramatic downward shift in the average molecular weight (m.w.) is observed after gel filtration under denaturing conditions (Sepharose 6B, 6 M guanidine hydrochloride or polyacrylamide gel electrophoresis containing 0.1 % sodium dodecyl sulfate). We conclude that under nondenaturing conditions, GAT is a multimeric structure; the dissociation of the structure is reversible. GAT was fractionated based on the size of the polypeptide chains under denaturing conditions. After removal of guanidine hydrochloride three fractions were obtained with ∼ 100 000 (GAT fraction I), 45 000 (GAT fraction II) and<10 000 (GAT fraction III) m.w., respectively.The immunological properties of these three fractions have been compared with those of unfractionated GAT. Fraction II resembles unfractionated GAT, showing similar immunogenicity in responder mice and suppressive properties in nonre‐sponder animals. Fraction I is less immunogenic, otherwise it resembles unfractionated GAT. Fraction III is the most dissimilar of the three fractions investigated. It retains the suppressive activity of GAT but is unable to stimulate a specific antibody response in responder animals. GAT fraction III is not a general tolerogen and is specifically suppressive for no

ISSN:0014-2980    

DOI:10.1002/eji.1830070207

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractPopulations of lymphocytes primed to alloantigensin vitroare stimulated by allogeneic cells which are unrelated to the specific stimulator cells used for priming. The number of lymphocytes in the primed population which responded to unrelated stimulators could be estimated in relation to the number of primed lymphocytes responding to the specific stimulator. This was done by measuring the responses of decreasing numbers of primed lymphocytes to various stimulator cell populations. Similar estimates were obtained on several occasions using the same combination of lymphocytes which were primed and retested at different times.There was a close correlation between the estimated frequency of lymphocytes in a primed population which responded to unrelated stimulators and the number of responder lymphocytes required to obtain a measurable response. Stimulators which activated a high frequency of primed cells required fewer responder lymphocytes than those which activated lower frequencies of primed cells. The specific stimulator was capable of initiating a response using fewer responder lymphocytes than were most unrelated stimulator cells. This confirms that primed populations are predominantly enriched for lymphocytes responding to the specific stimulator.At least some lymphocytes in a primed population responded to both the specific stimulator and unrelated stimulator cells. This was demonstrated in two types of experiments. In the first, it was possible to enrich lymphocytes in a primed population which responded to unrelated stimulator cells without depleting lymphocytes which also responded to the specific stimulator. In the second, primed lymphocytes from donor A, which showed strong reactivity to stimulators from donor D after priming with B stimulator cells, also showed significant reactivity to B stimulators after priming with D cells. These results strongly suggest that primed populations contain several subpopulations (clones) of lymphocytes whose specificities differ as exhibited by their responsiveness to unrelated stimulator cells.

ISSN:0014-2980    

DOI:10.1002/eji.1830070208

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractA sensitive radioimmunoassay for rabbit immunoglobulin allotypes has been developed. Separation of antibody‐bound and free antigen was accomplished by salt precipitation with ammonium sulfate, followed by collection and wash on glass fiber filters by means of a semi‐automatic cell harvester. The efficiency of the collection was increased by the addition of nonionic detergent which was salted out together with the precipitated reagents. The presentation of the a1 allotype, located in the VHregion, was found to be different on IgG and IgA molecu

ISSN:0014-2980    

DOI:10.1002/eji.1830070209

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractA radioimmunoassay with specificity for the al allotype determinant of rabbit immunoglobulin (Ig) heavy chains was used for the quantitation of VHin detergent extracts of lymph node cells from a1a1/b4b4rabbits. B cell‐derived Ig in the same extracts was estimated with a radioimmunoassay specific for L‐chain. About 2 × 105molecules/cell was found by both assays when assuming a molecular weight of 1.5 × 105dalton. Extracts prepared from lymphocytes depleted of B cells (surface Ig+cells) were also found to contain corresponding amounts of a1 and L‐chain, with values varying from about 103to 104molecules/cell. The estimates were not influenced by the presence of inhibitors of proteolytic enzymes. Supernatants, obtained after keeping the lymphocytes in culture for 16 h, were analyzed by the same methods. Again, matching amounts of a1 and L‐chain were found in supernatants from nonfractionated as well as from B cell‐depleted populations.The results obtained indicate that T cells do not carry or produce an excess of a1 compared to L‐chain, as would have been expected if the T cell antigen receptor carried the same variable region as the Ig heavy chain while being otherwise composed of nonimmunoglobulin‐

ISSN:0014-2980    

DOI:10.1002/eji.1830070210

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY

摘要:

AbstractDifferential velocity sedimentation was applied for separating alloimmune T lymphocytes bound to target cells (TC) from free lymphocytes. Maximal size differences between lymphocytes and TC were achieved a) by isolating the fraction of small peritoneal lymphocytes (SPL) from an alloimmune peritoneal cell population, and b) by selecting large tumor cells as TC. Under the conditions used, most of the conjugates formed at room temperature consisted of one SPL bound to one TC, and adequate separation of bound from free SPL could be achieved within less than 5 min.Functional studies of the conjugate‐enriched fractions showed that a minimum of 60 % of TC‐bound SPL were indeed cytolytic. Conjugate‐depleted fractions, however, were still lytic, suggesting that not all effector cells formed stable conjugates at room temperature. Transmission and scanning electron microscopy studies revealed that binding between SPL and TC was achieved through interpenetrating membrane projections and was characterized by point and broad zone contacts. When lysis was allowed to proceed, prominent changes of the TC membrane morphology, including loss of microvillous projections, appearance of localized blebs, pseudopod‐like projections, and membrane defects were doc

ISSN:0014-2980    

DOI:10.1002/eji.1830070211

出版商:WILEY‐VCH Verlag GmbH    

年代:1977

数据来源: WILEY