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Biomedical subjects

J F Miller

Publications and source records attributed to J F Miller.

At least 289 records · Page 16Linked to original sources
PubMed1979

I-region-coded products expressed on both macrophages and thymus epithelium influence T-cell activities.

I-region-coded products expressed on the surface of both macrophages (Mph) and thymus epithelium were shown to restrict T-cell activities at the level of antigen recognition and determination of the T-cell repertoire. Thus keyhole limpet haemocyanin (KLH) -pulsed Mph could elicit a delayed-type hypersensitivity response in a KLH-sensitized mouse only when the Mph and the sensitized mouse were compatible at the I-A region of the major histocompatibility complex. Also, experiments with thymus-grafted chimaeras showed that I-region compatibility between the thymus of the cell donor and the reticuloendothelial system of the recipient was essential for successful transfer of the DTH reaction. Thus, F1 T cells derived from stem cells differentiating in a P1 thymus graft, where F1 parents (P1 and P2) differed only at defined regions of the H-2 complex, could always transfer sensitivity to P1 mice. However, successful transfer to P2 mice was possible only if P1 and P2 were H-21-compatible.

Animals↗
PubMed1979

Influence of thymus genotype on acquisition of responsiveness in delayed-type hypersensitivity.

Antigen-pulsed macrophages (Mph) could sensitize syngeneic mice for delayed-type hypersensitivity (DTH) and also elicit sensitivity from mice sensitized to antigen in adjuvant provided these were syngeneic or semi-allogeneic to the strain providing the Mph. Sensitivity could not be elicited with antigen-pulsed allogeneic Mph. Antigen-pulsed Mph from low-responder (LR) strains could not sensitize LR mice nor F1 hybrids between responder (R) and LR strains. Normal F1 mice could be sensitized to respond to antigen presented on Mph or either parental type (i.e. P1 or P2): if, however, they were sensitized to antigen on P1 Mph, DTH transfer was restricted to naive P1 mice, not to P2 (restriction imposed by priming). F1 T cells derived from stem cells differentiating in a P1 thymus graft could be sensitized but could transfer sensitivity only to naive P1 mice, not to P2 (restriction imposed in thymus). When an antigen under Ir gene control was used, LR derived T cells differentiating in an (R X LR)F1 thymus could be sensitized but only if antigen was presented on (R X LR)F1 Mph not on LR Mph. Totally allogeneic chimaeras could be sensitized but only if given antigen in association with the appropriate Mph. These findings suggest that restriction of T cell activities can be imposed as a result of priming in some cases and as a result of differentiation within the thymus in others. LR strains appear to have a lesion at the level of antigen presentation by Mph; whether they also have a defect at the level of generation of T cell repertoire cannot be determined from the present investigations.

Animals↗
PubMed1979

Delayed type hypersensitivity to allogeneic cells in mice. I. Requirements for optimal sensitization and definition of the response.

Mice were sensitized to allogeneic cells under defined conditions, and their response to antigen deposition in the ear was measured by the influx of radioisotope-labeled cells. The delayed onset, T cell dependency and histology of the ear reaction were characteristic of delayed type hypersensitivity (DTH). Positive responses were obtained in a strain combination unable to elicit a mixed lymphocyte reaction (MLR), in B-Ly mice incapable of cytotoxic T lymphocyte (CTL) generation and in allogeneic combinations challenged with noncellular material. This suggests that MLR and CTL cannot, on their own, account for the response. Hence the ear reaction can best be explained in terms of DTH.

Animals↗
PubMed1979

Delayed type hypersensitivity to allogeneic cells in mice. II. Cell transfer studies.

Sensitivity to allogeneic cell surface antigens was transferred to naive mice by lymphoid cells from sensitized mice. Sensitivity was detected 24-48 h after antigen challenge and was associated with a mononuclear cell infiltration. The cells responsible for transfer were T lymphocytes as demonstrated by successful transfer with cell suspensions enriched for T lymphocytes, and by abrogation of transfer following treatment with anti-Thy-1.2 serum and complement. Both Lyl+ and Ly2+3+ bearing T cells were involved. Removal of Ia+ cells had no effect on the ability of sensitized lymphoid cells to transfer the reaction to naive mice.

Animals↗
PubMed1978

Specific suppressive factors produced by hybridomas derived from the fusion of enriched suppressor T cells and a T lymphoma cell line.

A cell fusion technique was used to produce hybridomas between the T lymphoma cell line, EL-4, derived from C57BL (H-2(b)), and an enriched population of human gamma globulin (HGG)-specific suppressor T cells prepared from the spleens of HGG-tolerant CBA mice (H-2(k)). Membrane fluorescence analysis of the hybridoma cells within 6 wk of cell fusion revealed expression of H-2(k) and I-J(k) gene products as well as H-2(b) antigens. Sonicates prepared from hybridomas which contained I-J(k) cells were tested for suppressive activity in vivo in irradiated mice given HGG-primed cells, dinitrophenyl (DNP)-primed cells, HGG-DNP, and horse erythrocytes. Among 18 such hybridoma lines, 6 showed specific suppressive activity, 5 nonspecific suppression, and 7 no suppression. Most lines progressively lost, with time, those properties derived from the normal parent cell. By about 3 mo after fusion few cells expressed CBA markers and only one cell line (number 77) retained some specific suppressive activity. In parallel with the losses was an alteration in chromosome number from near-tetraploid, soon after cell fusion, to near- diploid. Preliminary results with the T lymphoma-sensitive hypoxanthine aminopterin thymidine cell line, L5178, indicate retention of the expression of surface markers derived from the normal parent for 18 wk after hybidization. This suggests that T lymphoma cell lines may have to be screened for their capacity to produce hybridomas with stable properties.

Antibody Formation↗
PubMed1978

The frequency of clones of cytotoxic lymphocytes generated by H-2 antigens.

By using a culture system that allows the segregation of individual precursors of cytotoxic lymphocytes, the number of clones generated by cells from different combinations of congenic mice have been measured. It has been found that 0.3% of the total anti-H2d clones are generated by stimulators which differ predominantly at the H-2 locus. The contribution of non-H-2 antigens to anti-H-2 responses is discussed.

Animals↗
PubMed1978

T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction.

Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.

Animals↗
PubMed1978

"The child is father to the man": dependency in professional relationships.

This situation where two or more members of different professions are working jointly with the same client or patient is compared to the way the relationship between parents affects their children. It is suggested that stress inclines colleagues to infantile patterns of relationship, one partner being dominant and the other dependent. This is likely to detract from the service offered as a result of unwitting collusion and general evasion of responsibility. The need for adult or balanced patterns of professional dependency is argued and that this is as important to the patient's welfare as the type of treatment offered.

Humans↗
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↗
PubMed1978

Coexistent bullous pemphigoid and systemic lupus erythematosus.

A case of coexistent bullous pemphigoid and systemic lupus erythematosus is reported. Evidence for an immunologic pathogenesis is reviewed for both disorders. It is suggested that the coexistence of bullous pemphigoid and systemic lupus erythematosus may represent a similar pathomechanism.

Adult↗
PubMed1978

Specific suppression of the immune response by a factor obtained from spleen cells of mice tolerant to human gamma-globulin.

An antigen-specific suppressive factor was extracted from spleen cells of mice made tolerant by injection of deaggregated human gamma-globulin (HGG). The active material could be prepared from T cells, obtained by passaging spleen cells through an anti-immunoglobulin column, although not from cells adherent to the column nor from spleen cells pretreated with anti-Thy-1 serum and C. This factor was antigen-specific since it was retained on immunoadsorbents containing HGG, but not on columns coated with antibody to HGG or with irrelevant antigens. Despite its specificity for antigen it did not bear any classical immunoglobulin determinants. Its m.w. ranged between 30,000 and 55,000 daltons. It was a product of the I region of the major histocompatibility complex since it carried Ia determinants. The properties of this factor are very similar to those reported elsewhere for suppressive factors obtained from primed T cells, cells from nonresponder mice, and allotype-specific cells. This suggest the existence of a major class of immunoregulatory molecules, nonimmunoglobulin in nature, and responsible for the mediation of antigen-specific T cell-dependent suppression.

Animals↗