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S D Miller

Publications and source records attributed to S D Miller.

At least 253 records · Page 14Linked to original sources
PubMed1978

Suppressor T cell mechanisms in contact sensitivity. II. Afferent blockade by alloinduced suppressor T cells.

We investigated the mechanism(s) by which MHC-restricted suppressor T cells (Ts) induced by i.v. injection of allogeneic DNP-modified lymphoid cells (alloinduced Ts) suppress the DNFB contact sensitivity response. It was shown that alloinduced Ts acted only during the early phases (afferent limb) of sensitization. They were incapable of suppressing previously sensitized recipients or of inhibiting the expression of DNFB-immune LN cells when co-transferred into normal recipients. The target of alloinduced Ts seems to be cell proliferation, i.e., inhibition of antigen-induced cell proliferation (DNA synthesis) in Ts recipient mice. The failure of recipients of alloinduced Ts to generate DNFB-immune LN cells capable of transferring contact sensitivity to normal recipients also suggests that these Ts act by preventing the development of an expanded clone of mature immune T cells. The suppressive effects of alloinduced Ts also were inhibited by prior in vitro treatment with anti-TNP serum. The data are discussed in terms of current models of suppression, and are compared to mechanisms of suppression in other contact sensitivity models.

Animals↗
PubMed1977

Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants.

Genetic restrictions in generation and expression of hapten-specific suppressor cells for contact sensitivity were found. Dinitrophenol- (DNP) or trinitrophenol-modified mouse spleen cells (SC) induced suppressors in donors able to transfer suppression to normal recipients. When allogeneic DNP-SC were injected into BALB/c mice, cells were generated which were suppressive only in the allogeneic strain providing the DNP-SC. In contrast, when DNP-BALB/c-SC were injected into BALB/c mice, suppressors were generated which were active both in BALB/c and in allogeneic mice (e.g., CBA). This apparent absence of syngeneic major histocompability complex restriction may be explained by cross reactive T-cell receptors which are VH gene products.

Animals↗
PubMed1977

H-2 restriction of suppressor T-cell induction by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitization.

Studies using hapten-modified lymphoid cells as tolerogens for 1-fluoro-2,4-dinitrobenzene contact sensitization have shown that BALB/c(H-2d) mice can be made phenotypically tolerant by dinitrophenyl (DNP) on either syngeneic or allogeneic mouse lymphoid cells (DNP-LC). However, suppressor T-cell induction (Ts) in these mice (as demonstrated by adoptive transfer to syngeneic recipients) was restricted to H-2 identity between the DNP-LC and the donor mouse. It was also shown that identity at the right end of the H-2 complex was sufficient for Ts induction. In addition, this restriction was also demostrated in CBA (H-2 K) mice and for tolerance in the 1-chloro-2,4,6-trinitrobenzene contact sensitivity system using trinitrophenyl-modified lymphoid cells.

Animals↗
PubMed1977

A splenic requirement for the generation of suppressor T cells.

Tolerance to contact sensitization with DNFB may be induced by DNBSO3. This specific unresponsiveness may occur via one or both of two mechanisms--production of suppressor T cells or clone inhibition. We investigated the role of the spleen in this unresponsiveness. Splenectomized mice may be tolerized by i.v. injection of DNBSO3, but they are incapable of serving as donors of lymph node cells for transfer of tolerance to normal recipients. Kinetic studies indicated that the spleen must be present at least three days after tolerization in order to permit development of a significant number of suppressor cells in the peripheral lymph nodes. We interpret these results to indicate that 1) clone inhibition does not require the spleen, 2) the generation of suppressor T cells is dependent on the presence of the spleen, and 3) it is likely that tolerogens in this system induce suppressor cells in the spleen and some of these cells or their products leave the spleen to reach the peripheral lymph nodes.

Animals↗
PubMed1977

Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

Animals↗
PubMed1976

Bacteriology of the socket in patients with prostheses.

Fifty-two unilaterally enucleated patients were studied for symptoms, signs, and actual presence of bacteria in the socket and fellow eye. The majority (85%) of asymptomatic sockets were found to have a mixed culture of pathogenic organisms. Sockets had a significantly (P = .001) greater frequency of pathogenic organisms than the fellow eye. Cross contamination does not appear frequently but is a definite possibility. We recommend culture and treatment of the asymptomatic socket before surgery on the remaining eye.

Adolescent↗
PubMed1976

Requirements for induction of T cell tolerance to DNFB: efficiency of membrane-associated DNFB.

Tolerance to contact sensitization with DNFB, a T cell-dependent phenomenon, was induced in mice by preparations of DNFB coupled to mouse RBC or spleen cells. Such tolerance is dose related, wanes with time, and can be transferred to normal animals with lymphoid cells (presumably containing suppressors). Tolerance to DNFB-RBC can be produced by whole DNFB-RBC, by ghosts of these cells, by sonicates of the ghosts, and by detergent-treated DNFB-RBC ghosts. Tolerance cannot be produced by larger amounts of DNFB-RBC components not associated with membrane. The ability of various DNP compounds to stimulate DNA synthesis in DNFB-sensitized cells also correlates with their ability to bind to protein components; i.e., DNFB is a far more efficient stimulator than DNBSO, whereas DNPlysine does not stimulate at all. Thus, the ability to sensitize or to tolerize with DNFB congeners is related to their ability to couple to proteins. It appears that the active induction of T cell tolerance requires that tolerogen be coupled to cell membranes. Since both T cell sensitization and tolerance to DNFB are best produced by DNFB-membrane, the actual occurrence of one state or the other must depend on the molecular method of "presentation" of DNFB-membrane.

Animals↗
PubMed1976

The induction of hapten-specific T cell tolerance by using hapten-modified lymphoid cells. I. Characteristics of tolerance induction.

BALB/c mice were made tolerant to the T cell-dependent phenomenon of contact sensitivity to DNFB by i.v. injection of syngeneic lymphoid cells which had been previously modified with DNFB in vitro. The highly efficient unresponsiveness, as measured by ear challenge and in vitro antigen-induced cell proliferation, was shown to follow dose-response kinetics both in vivo and in vitro and to be exquisitely specific for the DNP moiety. The kinetics of tolerance induction were shown to be very rapid and had been previously shown to be long lasting. Unresponsiveness was more efficient when the hapten-modified cells were introduced by the i.v. route and tolerance could be increased by repeated injection of tolerogen. The tolerance could be transferred to normal syngeneic recipients by spleen and/or lymph node cells from tolerant donors. A wide variety of hapten-modified lymphoid cells, including mixed cell populations and enriched populations of T cells, B cells, and macrophages, were capable of inducing tolerance. The unresponsiveness was dependent merely on the association of DNP to the lymphoid membrane proteins and not upon the viability of the hapten-modified cells. These experiments support the hypothesis that in hapten-specific T cell sensitivity, as exemplified by contact sensitivity to DNFB, specific T cell tolerance in actively induced by hapten on self-membrane. In other hapten-specific antibody-forming systems, tolerance appears to be most readily induced by hapten on soluble self protein or on a nonimmunogeneic carrier.

Animals↗
PubMed1975

Phlyctenular keratoconjunctivitis: results of penetrating keratoplasty in Alaskan natives.

Corneal scarring secondary to inactive phlyctenular keratoconjunctivitis (PKC) is a significant cause of decreased vision in Alaskan Natives. The results of primary penetrating keratoplasty for such cases at the Alaska Native Medical Center form the basis of this report. Eighteen cases met the criteria established for this study. Fourteen (79 percent) had clear grafts at least six months after surgery (average follow-up: 46 months). Of the twelve grafts performed using 10-0 nylon and the operating microscope, 11 (92 percent) were clear. Twelve of the 14 persons with clear grafts had improved vision of at least two lines on the Snellen chart. On the basis of this report, penetrating keratoplasty for corneal scarring due to PKC seems to have a favorable prognosis.

Adolescent↗
PubMed1974

Effects of carbon dust inhalation on the cell-mediated immune response in mice.

The effects of carbon dust inhalation on the bone marrow-derived (B) and thymus-derived (T) lymphocyte populations of spleen and mediastinal lymph node (MLN) cultures were examined. The concanavalin A (Con A)-responsive cell population (T cells) in the spleen was found to be depressed after 7 days of pre-exposure to carbon dust. However, this effect was transient, and after 14, 21, and 28 days of pre-exposure to carbon dust, the Con A-responsive cells exhibited a 30 to 40% enhancement over control group responses. Conversely, Con A-responsive cells in the pooled MLN cultures exhibited depression, ranging from 22 to 33% below control group values, after 7, 14, and 28 days of pre-exposure to carbon dust. The lipopolysaccharide (LPS)-responsive cell population (B cells) in the spleens of carbon-exposed mice was found not to differ significantly from control group values after all times of pre-exposure. LPS-responsive cells in the MLN cultures exhibited enhancement, ranging from 49 to 74% above control values, after 14, 21, and 28 days of pre-exposure to carbon dust. The ability of carbon spleen cell cultures from carbon-exposed mice to undergo antigen induced blast transformation after sensitization with Mycobacterium tuberculosis H37Ra was also determined. Mice exposed to carbon dust inhalation 2 weeks before and 3 weeks after aerosol or subcutaneous immunization exhibited significantly enhanced ratios of transformation upon culture of their spleen lymphocytes with purified protein derivative of tuberculin.

Aerosols↗