Control of experimental contact sensitivity.
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Animals↗
Biomedical subjects
S D Miller
Publications and source records attributed to S D Miller.
Immunoregulation of contact sensitivity.
Contact sensitivity to dinitro-fluorobenzene in the mouse is a form of delayed-type hypersensitivity. This reaction is closely regulated. Tolerance to contact sensitivity is mediated by at least 2 mechanisms, tolerance without demonstrable suppressor cells and tolerance with suppressor T cells. Suppressor T cells can inhibit either the afferent limb of sensitization or the efferent (elicitation) phase. These cells probably operate via soluble suppressor factors and require auxiliary cells. The duration of contact sensitivity itself is controlled by another mechanism, which is antibody. This antibody is directed against the T cells responsible for the delayed hypersensitivity state (TDH), and down-regulate these cells. It is antigen-specific and has the properties of an antireceptor (anti-idiotypic) antibody.
Animals↗
Suppressive mechanisms involving sensitization and tolerance in contact allergy.
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Animals↗
Nature of hapten-modified determinants involved in induction of T cell tolerance and suppressor T cells to NDFB contact sensitivity.
Unresponsiveness to DNFB contact sensitivity induced by DNP-modified lymphoid cells (DNP-LC) is mediated by two separable pathways: a rapidly induced, long lasting inhibition of reactive T cell clones (donor tolerance), and a transient period of suppressor T cell (Ts) activity. The present report has examined the nature of the hapten-modified determinants responsible for the induction of these pathways by utilizing soluble DNP-LC cell lysate preparations as tolerogens. The results indicate that both DNP-modified MHC and non-MHC encoded determinants can mediate donor tolerance 7 days after tolerization. On the other hand, the induction of Ts requires DNP-modified MHC determinants, since DNP-LC lysates passed over lentil lectin or specific anti-H-2 immunoabsorbent columns lost their ability to induce Ts. Additional experiments showed that the injection of DNP-LC lysate compatible with the recipient strain at the H-2K and H-2D region of the MHC was sufficient for the induction of Ts. We propose that Ts induction involves the direct presentation of DNP-H-2 determinants to Ts precursors, whereas the induction of donor tolerance may involve host processing and presentation of DNP-modified membrane determinants in conjunction with host MHC structures.
Animals↗
The induction of tolerance to DNFB contact sensitivity by using hapten-modified lymphoid cells. III. Effects of hapten concentration on the ability of MLS-disparate cells to induce rapid unresponsiveness.
We investigated genetic restrictions in the induction of immediate tolerance to DNFB contact sensitivity in mice. Using spleen cells from various donor strains haptenated at 500 micro M DNFB, we were unable to detect any restrictions in tolerance induction in recipients that were either syngeneic or allogeneic to the donor strain. However, if the concentration of hapten used in the in vitro labeling was decreased (from 500 micro M to 2.5 to 5 micro M DNFB), differences in tolerogenesis between the various donor strain haplotypes were found. Haptenated spleen cells labeled with 5 micro M DNFB produced a profound level of unresponsiveness in allogeneic recipients but produced minimal tolerance in syngeneic animals. This tolerant state was shown to be antigen-specific and was not produced by unmodified allogeneic cells alone. Further genetic analysis demonstrated that an efficient tolerant state was produced when the donor of the tolerogen and recipient differed at the MLS locus rather than at either the MHC or minor regions. This phenomenon required viable, Thy 1-bearing cells in the haptenated donor population for efficient tolerogenesis to DNFB contact sensitivity.
Animals↗
Suppressor T-cell mechanisms in contact sensitivity. III. Apparent non-major histocompatibility complex restriction is a result of multiple sets of major histocompatibility complex-specific suppressor T cells induced by syngeneic 2,4-dinitrophenyl-modified lymphoid cells.
This report has examined the mechanisms by which major histocompatibility complex (MHC) non-restricted suppressor T cells (Ts), induced by the i.v. injection of 2,4-dinitropheny (DNP)-modified, syngeneic lymphoid cells (DNP-LC), suppress the passive transfer of contact sensitivity mediated by syngeneic and allogeneic immune delayed hypersensitivity T cells (TDH). In terms of suppression of syngeneic TDH, it was found that the suppressive action of the Ts was only blocked by pretreatment with soluble syngeneic DNP-LC membrane preparations. Monomeric DNP-lysine, polymeric DNP-protein conjugates, and syngeneic TNP-LC membranes did not inhibit Ts function. Further experiments showed that inhibition of syngeneic suppression could be achieved by DNP-modified-membrane preparations that were only H-2D-region compatible with the Ts donor. Thus, Ts antigen receptors in this system specifically recognize DNP-modified H-2D-region determinants. In contrast, it was found that pretreatment os syninduced Ts with syngeneic DNP-LC membranes did not inhibit the ability to suppress allogeneic TDH. However, pretreatment of Ts with DNP-allogeneic membranes which were H-2D-end compatible to the allogeneic target TDH eliminated their ability to suppress the specific allogeneic TDH, leaving intact suppression of syngeneic or third party TDH. It is proposed that perturbation of the immune system by i.v. injection of syngeneic NDP-LC leads to the induction of a polyclonal wave of DNP-specific Ts activity. Some members of this set of Ts recognize DNP-self MHC determinants with moderate affinity and are thus specifically inhibited after pretreatment with those DNP-self determinants. Other members of this set display receptors which cross-react with high affinity with DNP-allogeneic determinants and thus suppress allogeneic TDH cells. These allosuppressive clones can thus be specifically inhibited only by pretreatment with DNP-LC membranes, MHC-compatible with the target TDH. The data are discussed in terms of current models of T-cell cross-reactivity and T-cell-receptor recognition.
Animals↗
Active suppression of 1-fluoro-2,4-dinitrobenzene-immune T cells. Requirement of an auxiliary T cell induced by antigen.
We investigated T-T cell interactions in the suppression of contact sensitivity. Suppressor cells that block the efferent limb of sensitivity (Ts-eff) can inhibit the passive transfer of contact sensitivity mediated by 1-fluoro-2,4-dinitrobenzene immune cells (T DH). But, Ts-eff cannot block the passive transfer of TDH which comes from cyclophosphamide (Cy) pretreated sensitized mice. We interpret these results to indicate that lymph node cells from sensitized mice contain not only TDH but also another intermediate cell which is required for the suppression of TDH by Ts-eff. This intermediate cell is sensitive to cyclophosphamide and requires antigen activation for its development. It is sensitive to adult thymectomy and anti-brain associated theta serum and is therefore designated as an auxiliary T-suppressor cell (Ts-aux). It is not sensitive to splenectomy and it carries I-J determinants. Ts-aux are required for the activity of suppressors of the efferent limb (Ts-eff) but not of suppressors of the afferent limb (Ts-aff). Thus, in the feedback loops in contact sensitivity, the generation of Tdh is coordinated with the development of auxiliary Ts which are essential for the suppression of those TDH.
Animals↗
The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells.
A mouse model of cell-mediated immunity (CMI) and tolerance to protein antigens horse gamma globulin (HoGG) and cytochrome (Cyt C) was investigated. A reliable CMI response as measured in vivo by ear swelling or by an in vitro T-cell proliferation assay could be induced by one of two methods: (a) sensitization by antigen-complete Freund's adjuvant in the base of the tail, or (b) sensitization by s.c. injection of antigen coupled to syngeneic lymphoid cells. The in vivo response exhibited characteristic CMI parameters, delayed kinetics, and transfer by viable T cells. Prior i.v. injection of HoGG-modified lymphoid cells (HoGG-LC) or Cyt C-LC before sensitization resulted in a rapidly induced, dose-dependent, antigen-specific suppression of both in vivo and in vitro manifestations of the CMI response. In addition, tolerance in this system was transferrable by an antigen-specific suppressor T cell (Ts). The Ts were found to diminish the in vivo ear swelling reaction in recipient animals, but had no effect on the in vitro T-cell proliferative response of the recipients. In contrast to the rapid development of tolerance in donor mice (phenotypic tolerance), transferrable Ts were first demonstrable 4--7 d posttolerization. This latter result indicates that at least two mechanisms of tolerance are operative in this system: the rapid induction of clone inhibition of reactive T cells and the slower induction of Ts. These results indicate again that the mode of antigen presentation is crucial in determining the immunologic outcome. In these experiments, cell-bound proteins injected subcutaneously led to delayed hypersensitivity while the same antigens injected intravenously led to tolerance. These results are considered in the light of recent experiments which show that T cells recognize antigens on cells in association with major histocompatibility complex products. We believe the following pathways are involved. In sensitization via subcutaneous injection of HoGG-LC, antigen reaches the lymph node via lymphatic pathways which lead to immunogenic macrophage-associated presentation and the activation of delayed hypersensitivity T cells (TDH). In tolerization via intravenous injection of HoGG-LC, antigen (a) reaches the lymph node via the blood, probably directly meeting the TDH, preventing its subsequent activation by immunogenic HoGG (clone inhibition) and (b) reaches the spleen, also via the blood, activating suppressor T cells.
Animals↗
Posterior corneal crystalline deposits in benign monoclonal gammopathy: a clinicopathologic case report.
A 74-year-old woman had bilateral, deep stromal, patchy crystalline corneal deposits with the greatest density in the midperiphery. Visual acuity was 6/120 in the right eye and finger counting at 1 m in the left eye. Histological examination of the corneal button showed large, irregular amorphous masses in the posterior stroma. The deposits stained red with Masson's trichrome and were positive for protein with the Danielli stain. Stains for amyloid, copper, and lipid were negative. The immunoperoxidase stain was positive for polyvalent IgG and kappa light chains. Transmission electron microscopy disclosed electron-dense deposits with linear and honeycomb profiles. Laboratory investigations disclosed elevated serum and urinary IgG kappa light chain (Bence Jones protein) levels. Urinary amino acids were normal. The serum copper level was elevated. Antinuclear antibody was positive at a titer of 1:80. A bone marrow aspirate was normal, as were roentgenograms of the skull.
Aged↗
Persistent pupillary membrane: successful medical management.
Persistent pupillary membranes usually undergo considerable atrophy during the first year of life. A minimum pupillary diameter of 1.5 mm is necessary for normal retinal image formation. Mydriatics, fixation pattern determination, and occlusion therapy as indicated can obviate the need for coreoplasty in patients with an extensive persistence of the pupillary membrane. We successfully treated a patient who had an almost total persistence of the pupillary membrane.
Amblyopia↗
Binding of ovalbumin to mouse spleen cells with and without carbodiimide.
We studied the binding of ovalbumin (OVA) to mouse spleen cells. In the presence or absence of carbodiimide (ECDI), uptake increased with greater cell numbers, increasing OVA concentration and increasing time up to 60 min. Between 60 and 210 microgram OVA could be coupled with ECDI to 2 X 10(8) cells. In the absence of ECDI, however, OVA uptake was still appreciable, but appeared to be of low avidity as it did not occur in the presence of competing fetal calf serum. These experiments provide a basis for the use of protein coupled to autologous cells in the induction of immunologic tolerance.
Animals↗
Hemodynamics in teenagers and asthmatic children during exercise.
Seventeen normal teenagers and eight asthmatic children were studied during submaximal exercise on a bicycle ergometer. A modification of a noninvasive multiple gas rebreathing method was utilized for the estimation of pulmonary capillary blood flow (Qc), diffusing capacity (DL), oxygen consumption (VO2), functional residual capacity (FRC), and pulmonary tissue plus capillary blood volume (VTPC). Significant increases in Qc, DL, VO2, and heart rate occurred in both groups of subjects. Regression equation of Qc equaled 6.0 + 0.0078 VO2 (ml/min) in the teenagers and 3.39 + 0.0082 X VO2 (ml/min) in the asthmatic children. The values of DL as a function of VO2 in both groups were similar to previously reported data. No significant changes in FRC or VTPC occurred in either group during exercise. This method appears to be an acceptable noninvasive way of studying exercise physiology in healthy or sick children.
Adolescent↗
Inhibition of specific immune responses by feeding protein antigens. IV. Evidence for tolerance and specific active suppression of cell-mediated immune responses to ovalbumin.
We studied the effect of a single intragastric administration of ovalbumin (OVA) on the subsequent development of OVA-specific cell-mediated immune (CMI) responses in BDF1 mice. In animals fed OVA 7 days before subcutaneous sensitization with OVA-CFA, we observed a concomitant dose-dependent decrease in both the humoral and CMI responses specific for OVA. The CMI tolerance was found to be antigen-specific when assayed in vivo by ear swelling or in vitro by an antigen-induced T cell proliferation assay because OVA-fed mice responded normally to sensitization with horse gamma-globulin. It was also shown that either spleen or lymph node cells, but not serum, from OVA-fed donors transferred suppression to normal recipients. The transfer was mediated by antigen-specific suppressor T cells (Ts) that appeared to inhibit the induction phase (afferent limb) of the CMI response, since the Ts were only effective when transferred before or shortly after the onset of sensitization.
Animals↗
Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex.
Genetic restrictions governing the induction and expression of suppressor T cells (Ts) in tolerance to 1-fluoro-2,4-dinitrogenzene (DNFB) contract sensitivity were studied. Tolerance was induced by using 2,4-dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogen. Two kinds of Ts were found-those produced by DNP-LC syngeneic to the donor of the Ts (syninduced Ts), and those produced by DNP-LC allogeneic to the donor of Ts (alloinduced Ts). Studies employing congenic resistant mouse strains indicated that recognition of DNP-modified-major histocompatibility region determinants on the tolerogenic DNP-LC was essential for the induction of both types of Ts. Non-H-2 genetic background was irrelevant to Ts induction. Mapping studies indicated that induction of both syninduced and alloinduced Ts was associated with recognition of DNP-modified-MHC region determinants which map to the right of the H-2G region (i.e., H-2D gene products). Tolerization of donor mice with DNP-LC which were H-2D region compatible, but not with H-2K or I region compatible DNP-LC, was both sufficient and required for the induction of hapten-specific syninduced Ts. Tolerization of donor mice with DNP-LC which were incompatible only at the H-2D region was sufficient for the induction of alloinduced Ts. These Ts were capable of suppressing recipient mice only if the recipients shared the H-2D region with the strain providing the DNP-LC tolerogen, and were not capable of suppressing recipients sharing all but the H-2D region with the tolerogen.
Animals↗
Disseminated Hodgkin's disease with bilateral orbital involvement.
Hodgkin's disease was diagnosed in a patient by lymph node excision. Orbital infiltration was demonstrated by echography and computerized axial tomography. Subsequent orbital biopsy specimens showed lacrimal gland involvement with definite Reed-Sternberg cells.
Adult↗
Pupil cycle time in optic neuritis.
A thin slit-lamp beam illuminating the pupil margin produced clearly visible pupil oscillations. These oscillations were timed with a stopwatch, thus producing a measurement of the "pupil cycle time". The pupil cycle time was remarkably stable in various testing situations and repeatable within +/- 3% over extended periods of time. When the iris muscles were normally innervated and responsive, the pupil cycle time was dependent on the speed of conduction and the number and strength of optic nerve impulses. Pupil cycle time can be measured in most persons with active or inactive optic neuritis. In the few patients whose light reflex is so poor that the pupil cycle time cannot be measured, the inability to induce cycling can itself be taken as a definite abnormality of the light reflex arc. Only 5% of normal persons 12 to 50 years of age are expected to have a pupil cycle time in either eye longer than 954 msec, or a difference in pupil cycle time between the two eyes longer than 70 msec. Pupil cycle time was significantly longer in patients with optic neuritis, with a P-value less than .001. The pupil cycle time is similar to visual evoked response latency time in that it can detect and quantitate subclinical defects in optic nerve conduction time. Pupil cycle time is objective and quantitative for each eye individually. It is a fast, simple, and reliable clinic test of optic nerve function.
Adult↗
Edge-light pupil cycle time.
A thin slit-lamp beam illuminating the pupil margin produces clearly visible pupil oscillations. These oscillations can be timed with a stopwatch, thus producing a measurement of the "edge-light" pupil cycle time'. The pupil cycle time is remarkably stable in various testing situations and is repeatable within about +/- 3% over extended periods of time. Expected normal distribution and 95% confidence intervals are given in Table 3. When the iris muscles are normally innervated and responsive, the pupil cycle time is dependent on the speed of nerve conduction and the number and strength of optic nerve impulses. Only 5% of normal persons aged 12 to 50 years are expected to have a pupil cycle time in either eye longer than 954 ms or a difference in pupil cycle time between the two eyes longer than 70 ms.
Adolescent↗
Suppressor T cell mechanisms in contact sensitivity. I. Efferent blockade by syninduced suppressor T cells.
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Animals↗