bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bimodal expression of tumor necrosis factor-alpha in association with rat lung reimplantation and allograft rejection.
Authors: DeMeester S R , Rolfe M W , Kunkel S L , Swiderski D L , Lincoln P M , Deeb G M , Strieter R M 
Published: December 2022

Abstract
Lung transplantation has become a therapeutic option for a number of end-stage pulmonary disorders. Lung transplant recipients experience more complications due to acute and chronic allograft rejection as compared to recipients of other solid organs. We postulated that the generation of TNF-alpha plays a significant role in the pathogenesis of acute lung allograft rejection. To test our hypothesis, we used a RT1-incompatible rat lung allograft model and demonstrated the time course, cellular source(s), and major compartment(s) of TNF production during the course of lung allograft rejection. This model allowed for immunogenetic standardization and reproducibility of lung allograft rejection across disparate major histocompatibility barriers. TNF production was characterized at the whole animal, organ, cellular, and molecular levels, and was found to be compartmentalized and expressed in a bimodal fashion from the lung allograft during lung allograft reimplantation and maximal rejection. Lung allograft rejection was significantly attenuated in animals pretreated with neutralizing TNF antisera as compared to animals receiving control sera. These findings may provide interesting insight into the use of novel and specific therapeutic intervention(s) during periods of acute lung allograft rejection.
Fusion of human B cell lines with HIV-1 envelope-expressing T cells is enhanced by antigen-specific Ig receptors. Possible mechanism for elimination of gp120-specific B cells in vivo.
Authors: Golding H , Dimitrov D S , Blackburn R , Manischewitz J , Blumenthal R , Golding B 
Published: December 2022

Abstract
The possible contribution of Ag-specific Ig receptors on B cells to syncytium formation with HIV-1 envelope (env)-expressing cells was examined. A unique model system was designed that used anti-TNP/TNP interactions between a panel of TNP-specific human B cell lines and TNP-haptenated HIV-1 env-expressing T cells. The prototype B cell line 1:13 (CD4dull) produced few syncytia with vaccinia gp120/41-infected CD4- T cell effectors. However, TNP-haptenation of the HIV-1 env-expressing cells resulted in a five- to 10-fold increase in syncytium formation. The "enhanced" syncytia were blocked by OKT4A mAb, soluble CD4, anti-TNP serum, and TNP-BSA, suggesting a role for both CD4 and Ig receptors. In contrast, the number of syncytia formed between CD4+ CEM T cells and TNP-haptenated effectors was reduced by 30 to 40%, compared with the unhaptenated effectors, suggesting that a fraction of the TNP haptens bound close to the CD4 binding regions on the gp120 envelope, which was confirmed by other experiments. The possibility that B cells specific for the CD4 binding site on HIV-1 gp120 may be involved in syncytium formation with HIV-1 env-expressing cells was tested by screening a panel of five hybrid B cell lines from HIV-1-seropositive individuals. One of these lines produced anti-gp120 antibodies, which bound near the CD4 binding site, and also formed syncytia with HIV-1 env-expressing cells. This study suggests that, in addition to CD4 receptors, certain B cell Ig receptors that bind to gp120 may induce conformational changes leading to cell fusion and their elimination.
Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness.
Authors: Subramanyam M , Gutheil W G , Bachovchin W W , Huber B T 
Published: December 2022

Abstract
HIV-1 Tat has been shown to have an inhibitory effect on the Ag-specific responsiveness of human peripheral T cells. We have previously demonstrated that this retroviral protein binds to and partially inhibits the enzymatic activity of dipeptidyl aminopeptidase type IV (DP IV), also known as CD26, which is expressed on a variety of mammalian tissue, including T lymphocytes. A number of studies have implicated a role for DP IV in the activation of T lymphocytes. By utilizing HIV-1 Tat, as well as ProboroPro, a potent and specific boronic acid analog inhibitor of DP IV, we show here that blocking DP IV partially inactivates Ag and anti-CD3-mediated T cell proliferation. Neither mitogen nor anti-CD2 mediated proliferation of T lymphocytes, however, is impaired by blocking DP IV. The target molecule for the inhibition induced by both compounds was confirmed by the finding that soluble DP IV neutralized the reduced Ag responsiveness. The Ag-specific inhibition could be overcome by the addition of exogenous IL-2, suggesting that blocking or inactivation of DP IV results in a state of anergy, probably by interfering with the delivery or amplification of a signal necessary for IL-2 production. This is further substantiated by the finding that costimulation of human PBMC via the CD28 molecule, which initiates a non-TCR-dependent signaling pathway, overcomes the reduced Ag responsiveness induced by Tat and ProboroPro. The fact that ProboroPro has no impact on stimulation of T cells with PMA and ionomycin implies that blocking DP IV is influencing events before the activation of protein kinase C and Ca2+ flux. These results suggest that DP IV is necessary for amplification of signals generated by the engagement of the TCR-CD3 complex by nominal Ag.
Calcium oscillations in human T and natural killer cells depend upon membrane potential and calcium influx.
Authors: Hess S D , Oortgiesen M , Cahalan M D 
Published: December 2022

Abstract
With the use of single-cell digital imaging of the fluorescent Ca2+ indicator dye fura-2 we investigated Ca2+ signaling in human T lymphocytes and NK cells during activation by a variety of stimuli. A low percentage of resting T cells or T cell blasts displayed oscillations in cytosolic Ca2+ when stimulated with the mitogenic lectin PHA or by the addition of OKT3 mAb followed by a secondary cross-linking antibody. Lymphokine-activated T killer cells were more responsive than resting cells. A comparison of PHA, cross-linked anti-CD3, and a heteroconjugate mAb showed that at least 20% of the cells from these T cell preparations oscillated. Addition of PHA or cross-linked anti-CD16 caused NK cells to oscillate. In contrast, thapsigargin, a microsomal ATPase blocker, resulted in a relatively uniform, slowly rising and sustained Ca2+ response in all cell types studied. The maintenance of both thapsigargin- and receptor-induced responses required Ca2+ influx driven by a negative membrane potential. Because Ca2+ oscillations occurred in response to stimuli which mimic the normal activation of lymphocytes, and inasmuch as the percentage of oscillating cells increases with state of activation, these oscillations may play an important role in mitogenic activation.
Human T cell lines and clones respond to IL-9.
Authors: Houssiau F A , Renauld J C , Stevens M , Lehmann F , Lethe B , Coulie P G , Van Snick J 
Published: December 2022

Abstract
The activity of IL-9 on human T cells was investigated. Human T cell lines and clones, derived from PBMC by stimulation with PHA, IL-2, and irradiated allogeneic PBMC, were found to express a strong IL-9R message at the RNA level and to proliferate in the presence of IL-9, irrespectively of their CD4+ or CD8+ phenotype. Moreover, tumor-specific CTL clones also responded to IL-9. Contrasting with other T cell growth factors, such as IL-2, IL-4, or IL-7, IL-9 did not induce the proliferation of freshly isolated T cells. However, a significant proliferative response to IL-9 could be observed after a 10-day activation of PBMC with PHA, IL-2, and feeders. Taken together, our results indicate 1) that the activity of IL-9 on human T cells is wider than initially anticipated on the basis of the data obtained so far with murine cells; and 2) that proliferative responses to IL-9 require previous activation.
Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences.
Authors: Singer I I , Kawka D W , DeMartino J A , Daugherty B L , Elliston K O , Alves K , Bush B L , Cameron P M , Cuca G C , Davies P 
Published: December 2022

Abstract
The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4, yielding functionally equivalent humanized antibodies that are tolerated better in primates.
Comparison of antigen presentation of influenza A nucleoprotein expressed in attenuated AroA- Salmonella typhimurium with that of live virus.
Authors: Brett S J , Rhodes J , Liew F Y , Tite J P 
Published: December 2022

Abstract
Rationally attenuated strains of Salmonella expressing foreign proteins represent a potentially important vaccine delivery system. The characteristics of Ag presentation of influenza nucleoprotein expressed in an AroA- strain of Salmonella typhimurium (SL3262-pNP-2) have therefore been compared with those of soluble purified nucleoprotein (NP) and infectious influenza virus. This represents three distinct modes of internalization of the same protein into APC. Human monocytes and the monocytic leukemia cell line THP-1 infected with SL3261-pNP-2 were found to present several different epitopes from NP to human CD4+ class II-restricted T lymphocytes. Ag presentation to these T cell clones was enhanced by pretreatment of THP-1 cells with IFN-gamma but not TNF-alpha. Bacterial phagocytosis and Ag presentation of NP were increased after opsonization of Salmonella with immune serum. Macrophages infected with SL3261-pNP-2 were unable to present NP to class I-restricted T cells. In contrast, cells infected with live influenza virus, although recognized by NP-specific class I-restricted CTL, were inefficiently recognized by NP-specific class II-restricted T cells. Ag presentation to CD4+ T cell clones by monocytes of SL3261-pNP-2, purified recombinant NP, and live influenza virus, but not the synthetic peptide 206-229, was inhibited by chloroquine and the protease inhibitors pepstatin A and leupeptin, suggesting that the major route of processing in each case was via the exogenous pathway. T cell recognition of NP via all of these Ag delivery systems was also abrogated by cycloheximide and brefeldin A treatment, indicating a requirement for recently synthesized MHC class II molecules in presentation of whole NP after processing but not for the corresponding synthetic peptide.
Characterization of a recombinant T cell and B cell reactive polypeptide of Onchocerca volvulus.
Authors: Seeber F , Brattig N , Soboslay P T , Pogonka T , Lörz A , Strote G , Beck E , Titanji V P , Lucius R 
Published: December 2022

Abstract
To identify potentially protective Ag of the filarial nematode Onchocerca volvulus on the molecular level we screened a cDNA library of O. volvulus with a human serum raised against radiation-attenuated infective larvae of O. volvulus. A cDNA clone of 218 bp (OvL3-1) was selected for further studies. It was expressed in Escherichia coli and affinity purified recombinant polypeptide was tested for its ability to stimulate in vitro PBMC from African onchocerciasis patients and PBMC from chimpanzees experimentally infected with O. volvulus. An enhanced cell proliferation by PBMC was observed in many patients after stimulation with the recombinant OvL3-1 polypeptide. In addition, some patients' PBMC responded to OvL3-1 stimulation with enhanced IL-2 production. Infected chimpanzees also showed an increase in T cell proliferation. Onchocerciasis patients had variable levels of specific antibodies directed to the recombinant polypeptide when sera were tested by ELISA. A mAb directed against the recombinant protein located the native target Ag in the muscles of the adult worm. The molecular mass of native OvL3-1 was found to be 50 kDa on immunoblots. Polymerase chain reaction analysis of RNA from different life stages of the parasite showed that OvL3-1 is transcribed in all parasite stages within the mammalian host. A homologous gene is also present in other filarial parasites. The protein corresponding to OvL3-1, therefore, represents an immunogen present during the whole life-span of the parasite, and because of its B and T cell stimulatory properties, it may be a candidate for a protective Ag in human filariasis.
Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein.
Authors: Tobias P S , Soldau K , Kline L , Lee J D , Kato K , Martin T P , Ulevitch R J 
Published: December 2022

Abstract
Recent work has established that bacterial endotoxin (LPS) binds to the plasma protein LPS-binding protein (LBP) forming high affinity complexes (LPS-LBP), that LBP is an opsonin for LPS-bearing particles, and that LPS-LBP complexes are potent agonists for monocytic cells (MO). mAb to the MO plasma membrane protein, CD14, inhibit LBP-dependent binding of LPS to MO, and LPS-LBP-dependent stimulation of cytokine release from MO. These data suggest that CD14 functions as a membrane receptor for LPS but do not demonstrate a direct association of LPS with CD14. Calcitriol was used to induce a high level of CD14 expression in the human monocyte-like cell line THP-1, resulting in enhanced responses of these cells to LPS-LBP complexes manifested by enhanced binding of LPS and a decrease in the amount of LPS needed to induce IL-8 release. An Re595 LPS derivative containing a radioiodinated, photoreactive, phenyl azide (125I-ASD-LPS) was used in cross-linking experiments to identify membrane proteins in calcitriol-treated THP-1 cells that interact with LPS. 125I-ASD-LPS was added to calcitriol-induced THP-1 cells in the presence or absence of LBP, the mixture photolyzed, and the resultant radioiodinated proteins analyzed by SDS-PAGE and autoradiography. We observed strong cross-linking of 125I-ASD-LPS to a 55-kDa membrane protein when LBP was present, but failed to observe radiolabeling of any other proteins with apparent molecular masses distinct from CD14. The cross-linked product was identified as CD14 by immunoprecipitation with anti-human CD14 mAb. Studies with human CD14 expressing transfectants of the murine B cell line 70Z/3 also revealed LBP-dependent cross-linking of 125I-ASD-LPS to CD14. These data document binding of LPS to a specific membrane protein that serves as an LPS receptor.
Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells.
Authors: Egner W , McKenzie J L , Smith S M , Beard M E , Hart D N 
Published: December 2022

Abstract
Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.
SEB induced anergy: modulation of immune response to T cell determinants of myoglobin and myelin basic protein.
Authors: Gaur A , Fathman C G , Steinman L , Brocke S 
Published: December 2022

Abstract
Superantigens have the ability to stimulate a subset of T cells based upon their expressed TCR beta-chain. It has been demonstrated that the administration of staphylococcal enterotoxin B (SEB) in mice leads to unresponsiveness in V beta 8+ T cells in vivo which are the same T cells that could be stimulated in vitro by this enterotoxin. We present here data on the effect of SEB administration in DBA/2 and (PL/J x SJL)F1 mice on their T cell response to two different T cell determinants, the responses against which are dominated by the use of V beta 8+ T cells. Treatment of mice with SEB not only diminished their primary T cell proliferative response to these determinants, but also was able to effectively reduce the memory T cell response. SEB treatment, however, showed only a modest effect in preventing Ac 1-11-induced experimental autoimmune encephalomyelitis in H-2u mice.
The anti-idiotypic response by cynomolgus monkeys to humanized anti-Tac is primarily directed to complementarity-determining regions H1, H2, and L3.
Authors: Schneider W P , Glaser S M , Kondas J A , Hakimi J 
Published: December 2022

Abstract
The anti-ld response developed by cynomolgus monkeys to the humanized anti-Tac antibody was analyzed by using 12 humanized anti-Tac variants differing in V region structure. The majority of the monkey response was directed against idiotopes composed wholly or in part of complementarity-determining regions H1, H2, and L3. There was no detectable response directed solely to five single complementarity-determining regions examined or solely to the modified human V region framework.
CD28 delivers costimulatory signals for superantigen-induced activation of antigen-presenting cell-depleted human T lymphocytes.
Authors: Ohnishi H , Tanaka T , Takahara J , Kotb M 
Published: December 2022

Abstract
The CD28 pathway functions to provide costimulatory signals that are required for TCR-mediated activation of T cells. The role of this pathway in superantigenic stimulation of resting human T cells was investigated in the presence and absence of APC using a streptococcal superantigen, pep M5. Anti-B7/BB1 mAb inhibited the response of T cells when pep M5 was presented by APC. In the absence of APC, cross-linking CD28 by anti-CD28 mAb provides signals that synergize with APC-derived cytokines and with superantigen resulting in T cell proliferation. Anti-HLA-DR, -DQ mAb blocked the response of T cells to pep M5 presented by APC but had no effect on the response of purified T cells to the superantigen costimulated via CD28 cross-linking. These data show that the CD28 pathway is important for superantigenic stimulation of T cells and that signaling through this pathway can substitute for the APC-associated costimulatory activity that is essential for T cell stimulation. Moreover, the results are consistent with the notion that, in the presence of appropriate costimulation, pep M5 can directly interact with T cells and induce them to proliferate.
Mice treated with a leumedin or antibody to Mac-1 to inhibit leukocyte sequestration survive endotoxin challenge.
Authors: Burch R M , Noronha-Blob L , Bator J M , Lowe V C , Sullivan J P 
Published: December 2022

Abstract
Endotoxin challenge causes metabolic dysfunction mediated by TNF, and sequestration of leukocytes. NPC 15669, N-carboxy-L-leucine, N-[2,7-dimethylfluoren-9-yl)methyl] ester, inhibits leukocyte recruitment into inflammatory lesions in animals, and inhibits endotoxin-induced neutropenia and lymphopenia in mice. This study was carried out to determine whether the ability of NPC 15669 to inhibit leukocyte sequestration is sufficient to promote survival after endotoxin challenge. To inhibit leukocyte sequestration directly, mice were treated with anti-CD11a (LFA-1) or anti-CD11b (Mac-1) before endotoxin challenge. Anti-CD11b partly inhibited neutropenia and lymphopenia in response to challenge with LPS, but anti--CD11a had little effect on leukopenia. At doses of 100 and 1000 micrograms/kg, anti-CD11b increased survival to endotoxin challenge from 0 to 20 and 40%, respectively, whereas anti-CD11a was without effect. These observations, coupled with the finding that NPC 15669 does not inhibit endotoxin-induced TNF release suggest that inhibition of leukocyte sequestration can increase survival after endotoxin challenge, and that NPC 15669 or antibodies to Mac-1 may represent effective therapies for gram-negative sepsis and shock.