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M A Vadas

Publications and source records attributed to M A Vadas.

196 records · Page 11Linked to original sources
PubMed1979

A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni.

Centrifugation of human white blood cells over either Ficoll-Hypaque or slightly hypertonic Metrizamide discontinuous gradients reliably produces separate fractions that are enriched for either neutrophilic or eosinophilic granulocytes. This single step purification routinely yields 90 to 100% pure neutrophils and 85 to 100% pure eosinophils. Metrizamide gradients, in particular, reproducibly provide high yields of 90 to 100% pure eosinophils from normal subjects with 2 to 3% eosinophils in their peripheral blood. The method does not damage cells as judged by morphologic or functional criteria. The purified cell populations were tested for their ability to damage antibody-coated schistosomula either by the measurement of 51Cr release from labeled organisms, or by direct morphologic assessment. Neutrophils were superior in their ability to release 51Cr from labeled organisms, but eosinophils adhered to the organisms to a greater extent and induced microscopically detectable damage.

Animals↗
PubMed1978

Acquisition of murine major histocompatibility complex gene products by schistosomula of Schistosoma mansoni.

Schistosoma mansoni schistosomula recovered from the lungs of inbred mice were shown to possess serologically detectable alloantigens on their tegumental surfaces. Using appropriate antisera and infected congenic and recombinant mice as worm donors, gene products of the K and I subregions of the major histocompatibility complex were demonstrated among these alloantigens acquired by the parasites. In contrast, other cell surface alloantigens, such as Thy 1, Ly 1, and H-Y and the serum proteins albumin, C3 and Ig, could not be detected on the surface of lung schistosomula by means of comparable techniques. In another series of experiments, schistosomula recovered from the lungs of mice and reinjected into allogeneic recipients were shown to exchange their alloantigens during an 87-h period of examination. Similarly, lung schistosomula cocultured with allogeneic lymphocytes were shown to acquire major histocompatibility complex (MHC) coded antigens from the cells. It is possible that as acquired host molecules, MHC gene products may disguise the surface of schistosome parasites thereby rendering them insusceptible to immune attack.

Animals↗
PubMed1978

Major histocompatibility complex gene products on macrophages influence T cell activation.

Antigen-pulsed macrophages were used to sensitize or elicit sensitivity from mice of different strains to a variety of antigens. The results indicate that sensitization is directed, not to antigen as such, but to a complex structure on the macrophage surface determined partly by the antigen, and partly by a product coded by the major histocompatibility complex. Delayed type hypersensitivity could be provoked by antigen in responder (R) mice and in the F1 between responder and low responder (LR) strains, but not in LR mice unless pretreated by cyclophosphamide. Sensitivity could be transferred to naive LR-strain mice by lymph node cells taken 5 days after sensitization of cyclophosphamide-pretreated LR mice but not of F1 hybrids between LR and R strains. Sensitivity from these could be transferred only to naive F1 or R-strain mice. The results suggest that low responsiveness cannot be accounted for solely in terms of the operation of a cyclophosphamide-sensitive suppressor mechanism. It is postulated that antigen is less immunogenic when presented by LR-strain cells than by R-strain cells.

Animals↗
PubMed1977

Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes.

Delayed-type hypersensitivity (DTH) transfer to GAT was restricted by the I-A region of the major histocompatibility complex (MHC). Sensitized cells from F1 hybrid mice between responder and nonresponder strains transferred DTH to syngeneic F1 mice and to naive parental strain recipients of the responder but not of the nonresponder haplotypes. These results are interpreted to favor the postulate that the MHC-linked Ir genes exert their effects by coding for components which allow interactions between particular I region gene products and the region to form stable structures immunogenic for DTH T cells.

Alanine↗
PubMed1977

Antigen activation of T lymphocytes: influence of major histocompatibility complex.

There is considerable evidence that T-cell activation to soluble antigens occurs only if this is processed by macrophages and displayed appropiately on the cell membrane in association with products of the genes of the MHC. The genes responsible differ according to the cells and antigens involved. For cytotoxicity, targets and killer T cells must share K- or D-region gene products. For delayed-type hypersensitivity to FGG in mice, I-A identity is necessary; for DNFB, identity at either the I, K, or D region is sufficient. Experiments using three different approaches do not support the notion that these genetic constraints are due to the necessity for the T cell and stimulator cell to match an identical gene product or cell-interaction molecule. Rather, they favor the hypothesis that there are receptors on the activated T cell which recognize antigen and products of genes of the MHC. The implications of the results are discussed in terms of (1) different T-cell subsets, (2) the mode of action of Ir genes, and (3) the possible parallel evolution of T-cell receptors for antigen and gene products of the MHC.

Animals↗
PubMed1977

Studies on antigen-induced arthritis in mice. II. Immunologic correlates of arthritis susceptibility in mice.

Antigen-induced arthritis was developed in mice as a model of human rheumatoid arthritis by using methylated bovine serum albumin (mBSA) as antigen. It was found that most strains were susceptible, whereas CBA mice were resistant. We therefore investigated the humoral and cell-mediated immune responses to mBSA in resistant mice (CBA) and susceptible mice (exemplified by C57BL) to determine whether these were associated with susceptibility to arthritis. The resistant strain (CBA) differed from the suceptible strains in the following respects. First, there was a lower humoral immune response to mBSA as measured by passive hemagglutination, but this could be overcome by a larger immunogenic dose. Secondly, there were differences in response to low doses of DNP-mBSA after mBSA carrier preimmunization. Thirdly, there were striking differences in delayed-type hypersensitivity (DTH) to mBSA as determined by a radioisotopic assay in vivo; the response of CBA mice occurred early, at 5 days, declined quickly, and was weaker, whereas that of C57BL mice developed later and was long sustained. Genetic studies of the DTH response with hybrids and backcrosses showed an oligogenic control of immune responsiveness, with one gene being linked to the H-2b allele of the susceptible C57BL mice, and another being independent of the H-2 complex. Our findings indicate that in mice, susceptibility to antigen-induced arthritis with mBSA correlates with a higher responder state to this antigen, and that T cells are the major if not the only determinant of the high responder state.

Animals↗
PubMed1977

Studies on antigen-induced arthritis in mice. III. Cell and serum transfer experiments.

Antigen-induced arthritis in mice occurs after immunization and subsequent intraarticular challenge with methylated bovine serum albumin (mBSA). In adoptive transfer experiments, susceptible C57BL mice and resistant CBA mice were compared in their capacity to express delayed-type hypersensitivity (DTH) by ear assay, and to express arthritis. The expression of DTH could be transferred incrementally by lymphoid cells in C57BL mice, but not in CBA mice. Both immune lymphoid cells and, to a much lesser extent, serum transferred the capacity to develop arthritis in C57BL mice. The reactivity of transferred cells was abolished by anti-Thy-1 but enhanced by enrichment for T cells with anti-immunoglobulin columns. If this model disease can be equated with human rheumatoid synovitis, the lesions in the human disease would be an expression of a T cell-dependent activity.

Animals↗
PubMed1976

Ly and Ia antigen phenotypes of T cells involved in delayed-type hypersensitivity and in suppression.

The Ly and Ia phenotypes of T lymphocytes involved in different functions were characterized by the use of specific antisera. T cells responsible for delayed-type hypersensitivity (DTH) and for helper functions were found to be Ly-1+,2- in contrast to cytotoxic T cells and T cells responsible for suppression of antibody responses which were Ly-1-,2+. Unlike some primed helper cells, T cells involved in DTH were Ia-. Suppressor cells in the system were Ia+.

Animals↗
PubMed1976

Role of major histocompatibility complex gene products in delayed-type hypersensitivity.

Sensitized thymus-derived (T) lymphocytes can transfer delayed-type hypersensitivity (DTH) to naive mice only if there is identity at the major histocompatibility complex (MHC). The MHC region responsible differs according to the antigen used for sensitization. For transfer of DTH to fowl gamma globulin identity at I-A is necessary; for dinitrofluorobenzene, however, identity at either K, D, or I region is sufficient. T cells of one genotype, sensitized in a chimeric environment, transferred DTH to both parental strains even though these were MHC incompatible. However T cells from F1 hybrid mice, sensitized not in the F1 but in one parental strain, transferred DTH only to that parental strain, not to the other, in contrast to F1 T cells sensitized in the F1 which could transfer DTH to both parental strains. Macrophages pulsed with antigen in vitro could be used to sensitize syngeneic or semi-allogeneic mice for the transfer of DTH. Transfer was, however, successful only in the strain syngeneic to that from which the macrophages were derived. Evidence is also presented that genetically low-responder mice can be made to exhibit DTH provided they are pretreated with cyclophosphamide two days before sensitization. When considered in toto these results strongly argue in favor of the notion that there are receptors on activated T cells which recognize antigenic determinants and MHC gene products. The implications of these findings are discussed in relation to the role of macrophages in antigen presentation and to the possible parallel evolution of MHC gene products and of T cell receptors for antigen.

Animals↗
PubMed1975

H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.

Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.

Animals↗
PubMed1975

A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice.

Delayed type hypersensitivity (DTH) lesions have been difficult to evaluate objectively in the mouse because they are usually assessed in terms of an increase in footpad swelling or ear thickness. We have developed a radioisotopic method which not only reduces the observer's error but also gives an objective measurement of the cellular activity in the lesions. In brief, 10 mul of the test antigen is injected intradermally into the left pinna and either nothing or the same volume of a control solution into the right. 10 h later, a 2-muCi pulse of 5-iodo-2'deoxyuridine-125I is given intravenously, the ears cut off at the hairline 16 h later and the radioactivity counted in a gamma spectrometer. The following was obtained as evidence that the increased radioactivity of the left pinna over the right was a measure of the extent of a DTH response: (1) the ear reaction was delayed in mice without serum antibodies becoming maximum at 24 h; (2) there was a mononuclear cell infiltration in the left pinna and autoradiographs revealed radioactive label bound to these cells; (3) athymic mice could not develop a 24-hour ear reaction, and (4) antigens known not to activate T cells did not elicit the ear response. Cell transfer studies will be described in a subsequent paper. Different sensitization regimes were required with different antigens in order to obtain the highest levels of DTH as tested by the ear response, and the maximal ear reaction occurred at different days. The ear reaction showed the specificity expected of a DTH response.

Animals↗
PubMed1975

A radioisotopic method to measure delayed type hypersensitivity in the mouse. II. Cell transfer studies.

Sensitized lymphoid cells could transfer to normal non-sensitized (naive) mice by 24-48 h after antigen challenge in the ear, the capacity to incorporate, at the site of antigen deposition, 5-iodo-2'deoxyuridine-125I in amounts significantly above those obtained in control mice. This was associated with a mononuclear cell infiltration in the pinna. In contrast to lymphoid cells, serum antibodies were unable to transfer a 24- or 48 hour ear reaction. The cells responsible were T lymphocytes as demonstrated by successful transfer following enrichment for T lymphocytes, and abrogation of transfer following treatment with anti-theta serum and complement. Transfer was achieved whether the naive recipients were normal, T-cell deprived, pretreated with cyclophosphamide, or lightly irradiated but not when they were heavily irradiated. Adoptive transfer of the 24-hour ear response was demonstrated with three different antigenic systems. The time-response curves were different with each system although peak reactions were obtained 5 days after sensitization of the donors in all cases. The specificity patterns of the 24-hour ear reaction on transfer were similar to those obtained in the sensitized donors. The results of these studies indicate that the radioisotopic ear method can, under defined conditions, demonstrate the existence of a state of delayed type hypersensitivity in the donors.

Animals↗