bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization of rabbits with recombinant Treponema pallidum surface antigen 4D alters the course of experimental syphilis.
Authors: Borenstein L A , Radolf J D , Fehniger T E , Blanco D R , Miller J N , Lovett M A 
Published: December 2022

Abstract
Rabbits immunized with the protease resistant recombinant Treponema pallidum surface-associated Ag 4D showed an altered course of experimental syphilis after intradermal challenge with virulent T. pallidum. Vaccination trials using three different protocols were examined. In one experiment, a combined i.m.-i.v. immunization protocol was compared with an i.m. injection schedule. Four of five rabbits immunized by the i.m.-i.v. protocol developed morphologically atypical lesions at each of 16 sites, whereas the i.m. injected animals showed no evidence of attenuated disease. Moreover, immunization by both protocols elicited equally high ELISA titers of 4D-specific IgG antibody suggesting that cellular immune mechanisms may have been involved. In an effort to augment cell-mediated responses to 4D, seven rabbits received i.v. immunizations with an emulsion of 4D, purified BCG cell wall skeletons, and trehalose dimycolate in an oil-microdroplet form (4D-cell wall skeleton-trehalose dimycolate). Splenic lymphocytes from three representative immunized animals had a strong in vitro proliferative response to 4D as compared to controls. Further, all animals developed high anti-4D titers in response to immunization. After challenge with virulent T. pallidum, six of the seven rabbits developed an early cutaneous response (3-8 days) at the sites of inoculation consistent with a hypersensitivity reaction followed by morphologically atypical lesions. Aspirates from each of three representative atypical lesions were devoid of treponemes by darkfield examination at day 14, whereas motile T. pallidum were observed in aspirates from four of five control sites. Between days 20 and 24, lesions in the 4D-cell wall skeleton-trehalose dimycolate immunized rabbits began to enlarge and become more typical in appearance; aspirates from six of seven representative lesions were darkfield positive. We conclude that 1) immunization with the r4D Ag alters the course of experimental syphilis in a manner consistent with previously defined parameters of partial protection and 2) immunizations protocols containing an i.v. component are more effective than protocols using the i.m. route alone.
Strain-dependent expression of VH gene families.
Authors: Jeong H D , Komisar J L , Kraig E , Teale J M 
Published: December 2022

Abstract
The tremendous diversity of the antibody specificity repertoire stems from the ability of each developing B cell to select one out of many possible variable, diversity, and joining gene segments by specific rearrangement of the DNA. The mechanism by which V region gene segments is selected is not known. Moreover, evidence for both random and nonrandom expression of VH genes in mature B cells has been presented previously. In this report, the technique of in situ hybridization is used to accurately measure at the single cell level VH gene family expression in LPS-induced cells from several strains. In this way, at least one-third of the B cells are stimulated and a large sampling of activated splenocytes from each strain analyzed. The use of in situ hybridization eliminates any potential biases resulting from transformation protocols. In addition, because all populations of cells are analyzed by both in situ hybridization and immunocytochemical staining with anti-IgM, the proportion of cells detected by in situ hybridization could be compared with the proportion of B cells, blasts, and plasma cells in the population. It was concluded from these comparisons that the cells being detected by in situ hybridization under the conditions described are plasmablasts and plasma cells. Therefore, an accurate measure of the functional and expressed VH gene repertoire could be made. The results clearly demonstrate strain-dependent variation in VH gene family expression, particularly VH 7183 and VH J558 with up to three-fold differences observed. Thus, either there is considerable strain variation in the number of functional VH gene family segments or the expression of VH genes is not entirely random.
T15 PC-binding monoclonal antibodies retain specificity when they switch from IgM to IgG.
Authors: Spira G , Aguila H L , Scharff M D 
Published: December 2022

Abstract
The expression of some Ag-binding sites and their associated H and L chain V region genes are often dominated by one or another of the IgG subclasses. This is true of T15 anti-phosphorylcholine (PC) response in which the dominant T15 H (V1, DFL11.6 JH1) and L (VK22, JK5) chain V regions are seldom found associated with the gamma 2b or gamma 2a C regions in the circulation of BALB/c mice. In the present study we describe the characterization of gamma 2b, gamma 2a, and gamma 1 anti-PC antibodies obtained from IgM-producing hybridomas by Ig switching in culture. All switch variants retained the parental T15 idiotype, PC binding, and fine specificity. We thus conclude that the apparent in vivo restriction on the expressed T15 PC binding gamma 2 antibodies is not due to a conformational limitation on the expression of the anti-PC T15 binding site. Further, these studies confirm that in vitro switching can be used to generate mAb that are not readily available in vivo.
Relation between arachidonic acid metabolism and development of thymocytes in fetal thymic organ cultures.
Authors: Shipman P M , Schmidt R R , Chepenik K P 
Published: December 2022

Abstract
Because products of arachidonic acid metabolism, particularly the PG, have been implicated as modulators of growth and differentiation of adult thymocytes, we investigated relations between metabolism of arachidonic acid and growth, as well as differentiation, of thymocytes during fetal thymic organ culture. Fetal thymic cells synthesized immunoreactive PGE2 during organ culture and were found to be capable of metabolizing exogenous arachidonic acid to products that cochromatographed with authentic 6-keto-PGF1 alpha, PGE2, PGF2 alpha. Synthesis of these products and growth and expression of Thy-1 and Lyt-1 Ag were inhibited by culture of fetal thymic lobes with indomethacin, a cyclooxygenase inhibitor, as well as meclofenamate and eicosatetraynoic acid, inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Only indomethacin inhibited expression of Lyt-2. Culture with eicosatetraynoic acid also inhibited the capacity of thymic lobes to synthesize 15-hydroxyeicosatetraenoic acid-like products. The inhibitory effects of indomethacin on growth and expression of Thy-1 were partially reversed by simultaneous addition of arachidonic acid. Thus, fetal thymic cells appear to require an intact cyclooxygenase, and possibly lipoxygenase, pathway of arachidonic acid metabolism for growth and differentiation. These data also provide evidence that Lyt-1 and Lyt-2 may be regulated by different requirements with respect to arachidonic acid metabolism.
In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance.
Authors: Kelly E A , Colley D G 
Published: December 2022

Abstract
Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 (hybridoma GK 1.5) at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge (skin phase) still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.
Trypanosoma cruzi-induced suppression of IL-2 production. I. Evidence for the presence of IL-2-producing cells.
Authors: Tarleton R L 
Published: December 2022

Abstract
Mice infected with the protozoan parasite Trypanosoma cruzi, the causative agent of human Chagas' disease, are profoundly immunodepressed in their response to various Ag and mitogens. A key factor in this immunosuppression is the essential inability to produce the T cell growth factor IL-2. In this study we demonstrate that this failure to produce IL-2 in response to mitogen stimulation is not the result of the absence of production of soluble or membrane-bound IL-1 by macrophages. Limiting dilution analysis of the precursor frequency of IL-2 producers suggests that an adequate number of precursors for IL-2 production are present in the spleens of infected mice, but that their activity may be regulated by suppressor cells. The presence of precursor cells for IL-2 production is supported by experiments showing that the combination of calcium ionophores and PMA elicits IL-2 production by spleen cells from both normal and T. cruzi-infected mice. Although Con A can provide either of the signals necessary for IL-2 production, calcium flux or protein kinase C activation, to T cells from normal mice, Con A in combination with either calcium ionophore or phorbol ester failed to activate T cells from infected mice to produce IL-2. Preculture of spleen cells from infected mice for 48 to 72 h before addition of Con A results in near normal production of IL-2. This recovery of the capacity to produce IL-2 does not occur if parasite Ag is present during the preculture period. These results suggest that the inability of T cells from T. cruzi-infected mice to produce IL-2 in vitro in response to Con A is not due to the lack of IL-2-producing cells, but may be the result of the maturational state of the T cells or to the presence of a suppressor population.
In vivo and in vitro activation of pulmonary macrophages by IFN-gamma for enhanced killing of Paracoccidioides brasiliensis or Blastomyces dermatitidis.
Authors: Brummer E , Hanson L H , Restrepo A , Stevens D A 
Published: December 2022

Abstract
The fungicidal capacity of murine pulmonary macrophages (PuM) activated in vitro with IFN or lymphokines or in vivo with IFN was studied. PuM treated overnight with IFN (1000 U/ml), Con A-stimulated spleen cell culture supernatants, or lymph node cells plus Con A significantly killed yeast cells of the Gar w isolate of Paracoccidioides brasiliensis 45.5 +/- 2.1%, 72.0 +/- 4.2%, and 51.5 +/- 0.7% respectively. Two other isolates of P. brasiliensis (Ru and LA) were also killed (45 and 34%) by PuM activated by lymph node cells plus Con A. Control PuM had lesser but significant capacity for killing of P. brasiliensis isolates, ranging from 15 to 22%. Killing of P. brasiliensis by PuM activated by Con A-stimulated spleen cell culture supernatants could not be significantly inhibited by superoxide dismutase, catalase, or azide. When mice were treated in vivo with 4 X 10(5) IFN U i.p. and PuM isolated 24 h later, the PuM had significantly enhanced ability to kill P. brasiliensis (47.0 +/- 6.3%) compared with PuM from control mice (25.0 +/- 4.2%). PuM thus activated also showed enhanced killing (43%) of a second isolate compared with control PuM (22%). PuM from IFN-treated mice were able to significantly kill Blastomyces dermatitidis (37.5 +/- 0.7%) compared with control PuM (4.5 +/- 6.3%). These results show that PuM can be activated in vitro and in vivo by IFN for enhanced fungicidal activity against two pulmonary fungal pathogens and suggests that immunologic production of IFN could be an important factor in host defenses against these diseases.
Mechanism of protection from graft-vs-host disease in murine mixed allogeneic chimeras. I. Development of a null cell population suppressive of cell-mediated lympholysis responses and derived from the syngeneic bone marrow component.
Authors: Sykes M , Eisenthal A , Sachs D H 
Published: December 2022

Abstract
Splenocyte populations from whole body-irradiated recipients of mixed T cell-depleted (TCD) syngeneic and allogeneic (complete H-2 disparity) bone marrow, or of TCD syngeneic marrow alone, contain cells with the ability to suppress the generation of cell-mediated lympholysis responses in vitro. This activity, which is present by 8 days after bone marrow transplantation and persists for several weeks, has been analyzed for possible veto-like or other specificity. Although reproducible patterns of suppression were observed, depending both on host strain and on the genetic combination of the response examined, the overall suppression in vitro most closely resembles that which has been ascribed to "natural suppressor" cells in other systems. The suppression appears to be mediated by a non-T cell, non-B cell, nonadherent, asialo GM1-negative population. Cold target inhibition and CTL activity of chimeric cells have been ruled out as factors contributing to the observed suppression. Significantly, in mixed chimeras, suppression was found to be mediated exclusively by cells which were syngeneic to the recipient in both recipient strains tested. The rapid development of this suppressive activity may explain the resistance to graft-vs-host disease conferred on whole body-irradiated mice by the addition of TCD syngeneic marrow to an allogeneic graft-vs-host disease-producing inoculum.
Immunodeficiency in graft-versus-host disease. I. Mechanism of immune suppression.
Authors: Wall D A , Hamberg S D , Reynolds D S , Burakoff S J , Abbas A K , Ferrara J L 
Published: December 2022

Abstract
Irradiated CBA/J mice transplanted with H-2 compatible, minor histocompatibility disparate B10.BR bone marrow develop graft-versus-host disease (GVHD) if mature T lymphocytes are added to the marrow inoculum. In the setting of mild GVHD (receiving 10(4) or 10(5) T cells), by phenotypic analysis, lymphoid reconstitution occurs normally within 4 to 6 wk but there is a profound deficiency in the ability of splenic lymphocytes to respond to polyclonal activators such as LPS and Con A. This unresponsiveness is attributable to active suppression mediated by cells that express Thy-1 and can be removed with leucine methyl ester treatment. Thus, splenocytes from mice with GVHD suppress responses of normal T and B lymphocytes. Moreover, depletion of these suppressor cells restores normal function to splenocytes from mice with GVHD, and B cells isolated from these mice respond normally to T-dependent and -independent stimulation. Finally, IFN-gamma plays an important role in this suppression, because a neutralizing anti-IFN-gamma mAb significantly removes suppression of normal cells and restores functional responses of lymphocytes from mice with GVHD. These results provide insights into the mechanisms of immunodeficiency associated with GVHD, and suggest novel strategies for possible therapies for this disorder.
T-B collaboration in the in vitro anti-Sm autoantibody response of MRL/Mp-lpr/lpr mice.
Authors: Shores E W , Eisenberg R A , Cohen P L 
Published: December 2022

Abstract
Spontaneous production of autoantibodies to the Sm nuclear Ag is highly specific for SLE and the SLE-prone MRL mouse strains. Our previous studies have demonstrated that in vitro anti-Sm production in MRL/1pr mice requires the presence of T cells. In the present investigation, these T cells were found to express the L3T4+/Lyt-2- phenotype, unlike the aberrant L3T4-/Lyt-2-"double negative" 1pr T cells, and to utilize the L3T4 determinant in generating help for the anti-Sm response. The generation of anti-Sm did not require the presence of Sm-specific Th cells, as help could also be provided by T cells activated to an irrelevant Ag, or by nonspecific factors such as IL-2. There was no evidence for suppressor cell regulation of anti-Sm, even in animals negative for this specificity. These studies indicate that ongoing production of anti-Sm in MRL/1pr mice is dependent on the presence of T cells with a normal mature surface phenotype, and that these cells act in part through the elaboration of lymphokines. They further show that the anti-Sm status of individual MRL/1pr mice is not due to the action of suppressor cells. Because T cells appear to act primarily in a permissive fashion for the anti-Sm response, it is likely that events underlying the initial generation of Sm-specific B cell precursors are critical in determining whether an individual animal develops the Sm serologic specificity. Once these cells have arisen, clonal expansion of Sm-specific B cells may proceed in the presence of activated T cells or some of their products.
Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation.
Authors: Wahl S M , Hunt D A , Wong H L , Dougherty S , McCartney-Francis N , Wahl L M , Ellingsworth L , Schmidt J A , Hall G , Roberts A B 
Published: December 2022

Abstract
Transforming growth factor-beta (TGF-beta), a product of neoplastic and hemopoietic cells, is a bifunctional regulator of the immune response. At femtomolar concentrations, TGF-beta stimulates monocyte migration, and picomolar quantities induce synthesis of monocyte growth factors, including IL-1, that may promote tissue repair by regulating fibrosis and angiogenesis. Paradoxically, TGF-beta at picomolar concentrations also blocks the ability of IL-1 to stimulate lymphocyte proliferation. At 0.01 to 1.0 ng/ml, TGF-beta 1 and its homologue, TGF-beta 2, suppress the IL-1-dependent murine thymocyte proliferation assay. TGF-beta also inhibits human peripheral blood T lymphocyte mitogenesis. Inhibition of cell division appears to occur after activation of the lymphocytes inasmuch as neither gene expression nor translation of IL-2R is suppressed. Furthermore, TGF-beta does not block synthesis of IL-2. Therefore, TGF-beta 1 and TGF-beta 2 likely act at a site distal to IL-1 to block lymphocyte DNA synthesis. These findings suggest that TGF-beta secreted in an inflammatory site may be beneficial in diminishing lymphocyte function while promoting fibrosis and tissue repair. However, TGF-beta generated by neoplastic tissues may provide a mechanism for unrestricted tumor cell growth through its selective immunosuppressive effects.
Characteristics of a human monoclonal anti-Sm autoantibody expressing an interspecies idiotype.
Authors: Takei M , Dang H , Wang R J , Talal N 
Published: December 2022

Abstract
A human-human hybridoma secreting an anti-Sm mAb designated 4B4 was established by fusion of GM4672 (a lymphoblastoid B cell line) with PWM-activated mononuclear cells from a patient with active SLE. Competitive Ag inhibition assays showed that 4B4 was specific for Sm and did not bind with native or denatured DNA or RNA. Western blot analysis with 4B4 showed that this mAb binds to the B/B' ribonucleoprotein of the Sm/ribonucleo-protein complex. By competitive inhibition assay, 4B4 was demonstrated to partially share idiotypic expression with a mouse anti-Sm mAb designated Y2. This was demonstrated by the ability of each mAb (Y2 or 4B4) to inhibit a homologous anti-idiotypic antibody (either anti-Y2 or anti-4B4) better than the nonhomologous anti-idiotypic antibody. These results confirm previous findings that idiotypes related to Sm-binding are highly conserved in nature. Furthermore, this report is the first idiotypic analysis of a human anti-Sm mAb.
Absence of auto-antiidiotypic activity between the IgM and IgG fractions of human mixed cryoglobulins.
Authors: Stone G C , Nardella F A , Oppliger I R , Mannik M 
Published: December 2022

Abstract
Experimental animal models and observations in humans suggest that levels of Id and auto-anti-Id fluctuate reciprocally after Ag stimulation. In human monoclonal B cell disorders, however, the co-existence of paraprotein Id and its auto-anti-Id has been described in essential mixed cryoglobulinemia and in association with acquired C1 inhibitor deficiency. Because the majority of cryoglobulin IgM possess rheumatoid factor activity and thus bind the Fc region of IgG, we examined potential idiotypic interactions between cryoglobulin IgM and F(ab')2 fragments of autologous cryoglobulin IgG fractions. A rabbit antibody to the pepsin agglutinator site of human F(ab')2 was used as detection reagent. By recognizing epitopes exposed on F(ab')2 after the removal of Fc determinants by pepsin digestion, this reagent eliminates the detection of contaminating intact IgG. In a sensitive assay, we were unable to detect idiotypic interactions between the separated IgM and pepsin-digested IgG fractions of 10 mixed cryoglobulins. On the basis of these results, we suggest that in mixed cryoglobulinemia, the coexistence of paraprotein Id and its auto-anti-Id is unlikely.
Stimulation of eosinophil adherence to human vascular endothelial cells in vitro by platelet-activating factor.
Authors: Kimani G , Tonnesen M G , Henson P M 
Published: December 2022

Abstract
111In-Labeled eosinophils from mildly eosinophilic subjects have been examined for their capacity to adhere to cultured human umbilical vein endothelial cells. In assay buffer alone, 32.0% +/- 2.6 eosinophils adhered spontaneously to endothelial cells. Platelet-activating factor (PAF) (1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) at concentrations as low as 10(-9) M increased this adherence to a level of 46.7% +/- 2.0. The effects of PAF were confirmed to be on eosinophils by parallel adherence assays done on serum-coated plastic plates where comparably enhanced adhesion of the eosinophils was seen. Lyso-PAF, the biologically inactive precursor/metabolite of PAF, had no stimulatory properties. FMLP caused an increase in eosinophil adherence, comparable to that of PAF, but only at high concentrations (10(-6) to 10(-7) M). Further examination of eosinophil subpopulations separated on metrizamide gradients indicated that "hypodense" eosinophils had a significantly higher ability to adhere spontaneously to endothelial cells than "normal" dense eosinophils, (35.5% +/- 4.2 vs 23.8% +/- 2.5, respectively) and could be stimulated with PAF to higher levels, although the magnitude of stimulation was similar for both populations. A mouse mAb TS1/18 to the common beta-subunit of the Mac-1 cell surface glycoprotein complex (CDw18) reduced by up to 94.6% the PAF-induced increase in adherence, but had no effect on the spontaneous adhesion. Eosinophils were also shown by cytofluorography to be capable of binding the TS1/18 antibody on their cell surface, and in some experiments to exhibit an increased expression of the Mac-1 complex on stimulation with PAF. These studies indicate that eosinophils are capable of binding to endothelial cells in culture, that PAF is a potent stimulator of eosinophil adherence, and that the Mac-1 complex has a critical role in this adhesion process.