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Biomedical subjects

J F Miller

Publications and source records attributed to J F Miller.

At least 307 records · Page 17Linked to original sources
PubMed1977

Enrichment of specific suppressor T cells and characterization of their surface markers.

A simple method is described which allows antigen-specific suppressor T cells to be enriched by greater than 100-fold. The enriched cells have the following characteristic markers: Ig-, Thy-1+, Ly-1-, Ly-2,3+, and I-J+. More than 30% of this population could be killed directly by an antiserum specific for the I-J subregion gene product in the presence of complement.

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↗
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

Effect of recent antigen priming on adoptive immune responses. III. Antigen-induced selective recruitment of subsets of recirculating lymphocytes reactive to H-2 determinants.

Information was sought on the reactivity of thoracic duct lymphocytes (TDL) from parental strain mice injected intravenously with large numbers of irradiated semiallogeneic spleen cells. TDL collected at 1 day after spleen cell injection were almost totally depleted of lymphocytes able to produce cell-mediated lympholysis (CML), a graft-versus-host (GVH) reaction, and skin allograft rejection against the H-2 determinants on the injected spleen cells. Normal or near normal responses were observed against third-party determinants. In the case of CML, there was no evidence that the unresponsiveness was due to suppressor cells. In marked contrast, the capacity of TDL to exert a specific mixed lymphocyte reaction (MLR) against the injected determinants was reduced by no more than two to fourfold; this applied whether MLR were measured in vivo or in vitro. Injection of normal rather than irradiated semiallogeneic spleen cells gave similar results. Complete and specific removal of MLR-producing lymphocytes was achieved, however, in a different system in which parental strain T cells were filtered from blood to lymph through irradiated F1 hybrid mice. Since this system presumably provided a much higher concentration of H-2 determinants to the responding lymphocytes, it is suggested that the differing results obtained with these two systems may indicate that certain cells reactive to H-2 determinants are of low affinity, their reactivity being detected in the MLR, but not by other parameters. With both systems, MLR-producing lymphocytes reappeared in the lymph after 2-3 days; the cells collected at this stage gave an MLR of altered kinetics. The present data, in toto, suggest that under certain conditions of antigen presentation, virtually all recirculating lymphocytes reactive to a given set of H-2 determinants can be induced to leave the circulation for a period of 1-2 days. After responding to the injected determinants (presumably in organs such as the spleen), the cells re-enter the circulation in an activated state after 2-3 days.

Animals↗
PubMed1976

The nature of the cells generating B-lymphocyte colonies in vitro.

B-lymphocyte colonies are grown in semi-solid agar from mouse spleen or lymph node cells in the presence of mercaptoethanol with or without added sheep red cells. High levels of colony-forming cells were present in the spleen or normal mice and nu/nu (athymic) mice but colony-forming cells were rare in the thymus and not detected in activated T-lymphocyte populations. Colony-forming cells were theta-negative and most exhibited Fc receptors. Most colony-forming cells had the sedimentation velocity of small lymphocytes, were non-adherent and had a buoyant density similar to B-lymphocytes. Colony-forming cells were radiosensitive (Do60 rads) and sensitive to cortisone. Colony formation was potentiated by the addition of adherent spleen cells or peritoneal macrophages. It is concluded that most cells forming B-lymphocyte colonies are themselves characterisable as B-lymphocytes.

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↗
PubMed1976

Graft-versus-host reactivity and renal allograft survival in rats given allogeneic spleen cells or spleen allografts.

Selective recruitment of antigen-sensitive cells (ASC) into the spleen as a method of inducing specific suppression was attempted by intravenous injection of either DA or Lewis spleen cells 24 hr before a (DA X Lewis)F1 renal allograft into a Lewis or DA recipient, either with or without a splenectomy. This led to suppression of rejection in the DA recipient and delayed rejection in the Lewis recipient. Splenectomy produced a minimal augmentation effect. Assay of graft-versus-host (GVH) reactions in (DA X Lewis)F1 rats by a popliteal node assay showed that injection of allogeneic DA or Lewis spleen cells 48 hr before the assay significantly reduced the reaction produced by node lymphocytes but not spleen lymphocytes, suggesting a loss of ASC from the lymph nodes. Lewis spleen allografts did not produce such a significant reduction in the GVH reactivity of DA node lymphocytes as intravenous Lewis cells, whereas DA spleen allografts led to an increased GVH reactivity of Lewis node lymphocytes. From these studies, it is not possible to attribute the suppression produced by the intravenous injection of allogeneic cells to selective recruitment of antigen-sensitive cells to the spleen.

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