bluuebunny/crossref_metadata_2025_split huggingface dataset:
Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes.
Authors: Suzuki G , Moriyama T , Takeuchi Y , Kawase Y , Habu S 
Published: December 2022

Abstract
To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.
Induction of anti-double stranded DNA antibodies in normal mice by immunization with bacterial DNA.
Authors: Gilkeson G S , Grudier J P , Karounos D G , Pisetsky D S 
Published: December 2022

Abstract
Because of recent observations suggesting that bacterial DNA is immunogenic, the induction in normal mice of antibodies to Escherichia coli (EC) dsDNA was investigated. BALB/c and C57BL/6 mice were immunized with dsEC or ds calf thymus (CT) DNA complexed to methylated BSA in adjuvant; antibody responses were measured by ELISA. In both strains, dsEC DNA immunization induced a much higher anti-dsDNA response to dsEC DNA than did dsCT DNA immunization. Neither immunized group showed an appreciable antibody response when tested on dsCT DNA. Anti-dsDNA antibodies were also demonstrated by ELISA using synthetic DNA duplexes as well as a filter binding assay using 3H-labeled dsEC DNA as Ag. These results suggest that bacterial dsDNA is immunogenic and that at least some anti-dsDNA specificities can arise by immunization.
Promotion of human T lymphocyte proliferation by IL-4.
Authors: Mitchell L C , Davis L S , Lipsky P E 
Published: December 2022

Abstract
The capacity of human rIL-4 to support the proliferation of mitogen-stimulated T cells directly as well as by increasing IL-2 production or enhancing IL-2 responsiveness was investigated. IL-4 augmented proliferation of T cells stimulated with PHA, Con A, immobilized mAb to the CD3 molecular complex (OKT3), or PMA. IL-4 increased the number of mitogen-stimulated cells entering the cell cycle as well as enhancing ongoing proliferation of mitogen-activated lymphoblasts. Facilitation of initial activation by IL-4 was not inhibited by mAb to the p55 component of the IL-2R, anti-Tac, and, therefore, was not dependent on endogenous IL-2 activity. However, IL-4-mediated enhancement of ongoing T cell proliferation stimulated by PHA or OKT3 was partially but not completely blocked by anti-Tac. Analysis of the supernatants from PHA-stimulated T cell cultures indicated that IL-4 increased the production of IL-2 by mitogen-activated cells. Moreover, IL-4 increased the amount of IL-2 mRNA that accumulated in mitogen-stimulated T cells. In addition, IL-4 markedly augmented IL-2R expression by PHA-stimulated T cells. Although IL-4 promoted ongoing DNA synthesis of mitogen-stimulated T cells in an IL-2-dependent manner, it was also able to sustain their proliferation directly. Thus, IL-4 supported proliferation of PMA-activated T cells in a manner that was not inhibited by anti-Tac. Furthermore, IL-4 could augment proliferation and IL-2R expression of T cells stimulated with PHA in the presence of cyclosporin A, which blocks endogenous cytokine production or anti-Tac. Finally, IL-4 was noted to enhance proliferation of both CD4+ and CD8+ T cell subsets. The results indicate that IL-4 enhances proliferation of mitogen-activated human T cells by a number of mechanisms, including the direct promotion of cell cycle entry and subsequent DNA synthesis, enhanced production of IL-2, and increased responsiveness to IL-2 in part by up-regulation of IL-2R expression.
Genetic diversity of murine rheumatoid factors.
Authors: Duchosal M A , Kofler R , Balderas R S , Aguado M T , Dixon F J , Theofilopoulos A N 
Published: December 2022

Abstract
Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity. RF from arthritic mice expressed Vk messages from the overlapping Vk22 and Vk28 gene families more frequently than did those from nonarthritic mice. RF from autoimmune MRL mice, both arthritic MRL-lpr/lpr and nonarthritic MRL-+/+, showed skewed JH4 segment usage, whereas those from C57BL/6-lpr/lpr preferentially expressed JH2.
Molecular analysis of the HLA class II genes in two DRw6-related haplotypes, DRw13 DQw1 and DRw14 DQw3.
Authors: Kao H T , Gregersen P K , Tang J C , Takahashi T , Wang C Y , Silver J 
Published: December 2022

Abstract
We have compared the sequence polymorphism of HLA class II genes of two distinct DRw6 haplotypes. cDNA libraries were constructed from two lymphoblastoid cell lines: CB6B (10w9060) which types as DRw13 DQw1, and AMALA (10w9064) which types as DRw14 DQw3. Multiple sequence differences were found at the DR beta I, DQ alpha, and DQ beta loci when these two haplotypes were compared. The DR beta I allele found in the DRw14 DQw3 haplotype appears to have diverged primarily as a result of a gene conversion event with a DR1 allele acting as donor. In contrast, the DRw13 DQw1 haplotype appears to have arisen by means of a recombination event between the DR and DQ subregions. Thus, multiple genetic mechanisms, including point mutation, gene conversion, and recombination, have generated diversity among DRw6 haplotypes.
Generation and characterization of purified adherent lymphokine-activated killer cells in mice.
Authors: Gunji Y , Vujanovic N L , Hiserodt J C , Herberman R B , Gorelik E 
Published: December 2022

Abstract
During the incubation of murine spleen, lymph node, or bone marrow cells with IL-2 (1000 U/ml) a small percentage of cells became adherent to the surface of plastic tissue culture flasks. After removal of the non-adherent lymphoid cells, plastic adherent lymphokine-activated killer (LAK) cells could be efficiently expanded in the presence of IL-2. Plastic adherent-derived A-LAK cells were characterized by high rates of proliferation and their cytotoxic activity was more than 10 fold higher than LAK cells generated in the bulk (unfractionated) spleen cell cultures. A-LAK cells could be continuously generated from the non-adherent cell population. Using multiple transfers (every 1 to 2 days) of non-adherent LAK cells into new flasks, new rounds of plastic adherent cells were generated with high expansion capability and high levels of cytotoxic activity. Morphologically, A-LAK cells were large granular lymphocyte and phenotypically expressed markers characteristic of NK cells (asialo GM1+, NK1.1+, Qa5+, Ly-6.2+, Thy-1.2+, but negative for Lyt-2.2 and L3T4). A-LAK cells generated from mice of different strains expressing low and high levels of NK cell activity were equally highly cytotoxic. However, A-LAK cells obtained from nude or beige mice had relatively lower levels of cytotoxicity. Stimulation of NK cell activity by poly I:C or inhibition by in vivo or in vitro treatment with anti-asialo GM1 serum did not affect the generation of A-LAK cells. A-LAK cells derived from spleen or bone marrow of C57BL/6 or nude mice treated with anti-asialo GM1 serum were found to be asialo GM1+ suggesting that A-LAK cell could be generated from the asialo GM1- precursor cells. Expansion of plastic adherent A-LAK cells in the presence of IL-2 could provide large numbers of highly purified cytotoxic A-LAK cells suitable for cancer immunotherapy.
Requirement for delivery of signals by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T cell proliferation. Effectiveness of IFN-gamma modulation of accessory cells for physical interaction with T cells.
Authors: Kawakami K , Yamamoto Y , Kakimoto K , Onoue K 
Published: December 2022

Abstract
We analyzed the mechanism by which accessory cells support the induction of the proliferation of human peripheral blood T cells by a monoclonal anti-CD3 antibody, OKT3. Cross-linking of T cell receptor/CD3 complex by anti-CD3 coupled to latex beads and the addition of IL-1 are not enough to induce the IL-2 production and proliferation of T cells extensively depleted of accessory cells, while the addition of both the culture supernatant of macrophages or a monoblastic cell line, U937 cells, and the paraformaldehyde-fixed macrophages or U937 cells which had been precultured with interferon-gamma before fixation into the culture of the T cells with anti-CD3-latex did induce the T cell proliferation. Lack of the addition of either one of these did not induce the response. These results indicate that the signal(s) delivered by soluble factors released from the accessory cells and that delivered by the physical interaction between accessory cells and T cells are both required for the induction of IL 2 production and proliferation of T cells by anti-CD3-latex. Importantly, the macrophages or U937 cells had to be cultured with Con A-stimulated lymphocyte culture supernatant or IFN-gamma prior to fixation with paraformaldehyde, suggesting that a molecule(s) inducible on accessory cells surface by IFN-gamma or other lymphokine is necessary for the effective accessory cell-T cell interaction to induce the T cell response. It was further revealed that the activity of the culture supernatant of accessory cells may be mediated synergistically by IL 1 and a certain other factor(s) and was actually shown to be replaced by the combined addition of rIL-1 and rIL-6 but not by rIL-1 alone. The experimental system described here will be very useful for dissecting the accessory functions for T cell activation.
IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines.
Authors: Kirnbauer R , Köck A , Schwarz T , Urbanski A , Krutmann J , Borth W , Damm D , Shipley G , Ansel J C , Luger T A 
Published: December 2022

Abstract
IL-6, which is also known as IFN-beta 2, hybridoma growth factor, hepatocyte-stimulating factor, and B cell differentiation factor, mediates acute phase responses including fever, has lymphocyte-stimulating capacities, and antiviral activity. IL-6 is produced by monocytes, fibroblasts, certain lymphocytes, and various tumor cells. The present study demonstrates that this multifunctional cytokine is released also by normal human epidermal cells (EC) and human epidermoid carcinoma cell lines (A431, KB). Accordingly, supernatants derived from freshly isolated EC, long term keratinocyte cultures, A431, or KB cells stimulated the proliferation of a hybridoma growth factor/IL-6-dependent plasmacytoma cell line (B9). IL-6 constitutively was produced in the presence of serum proteins. The addition of IL-1 alpha, IL-1 beta, or the tumor promoter PMA significantly enhanced the synthesis and release of EC-derived IL-6 (EC-IL 6). Like monocyte or fibroblast-derived IL-6, EC-IL-6 exhibited Mr microheterogeneity within 21 and 28 kDa. Similarly in Western blotting experiments an antiserum directed against human rIFN-beta 2/IL-6 detected the different Mr forms of EC-IL-6. Moreover, this antiserum was able to block the B9 cell growth-promoting capacity of EC-IL-6 strongly suggesting that this EC-derived mediator is closely related, if not identical with IL-6. This was further confirmed by Northern blot analysis detecting IL-6 specific mRNA both in long term cultured keratinocytes and A431 cells by hybridization with a cDNA fragment encoding for B cell differentiating factor 2/IL-6. Therefore, in addition to the production of other cytokines as previously reported, EC and in particular keratinocytes also synthesize and release IL-6. This further supports the important regulatory role of the epidermis during the pathogenesis of inflammatory, autoimmune, and neoplastic diseases.
Protective effects of IL-1 on human hematopoietic progenitor cells treated in vitro with 4-hydroperoxycyclophosphamide.
Authors: Moreb J , Zucali J R , Gross M A , Weiner R S 
Published: December 2022

Abstract
Based on recently published data, IL-1 has been shown to provide radioprotective effects when given to mice 20 h before a lethal dose of irradiation and to enhance granulocyte recovery in mice treated with cyclophosphamide. In this study, we have investigated whether IL-1 can provide protection for human bone marrow colony-forming cells treated with high doses of 4-hydroperoxycyclophosphamide (4-HC), a potent derivative of cyclophosphamide. We have established an in vitro model system which demonstrates that prior incubation with IL-1 protects early human hematopoietic progenitor cells from the lethal effects of high doses of 4-HC. These early progenitors give rise to blast cell colonies which appear late in the culture and are characterized by their ability to give rise to different types of secondary colonies when replated. Furthermore, prior incubation with IL-1 was shown not to protect HL-60 or K562 leukemic cells from the lethal effects of 4-HC. We conclude that IL-1 is able to protect early human hematopoietic progenitors from a non-cell cycle-specific chemotherapeutic agent such as 4-HC, whereas providing no protection for the leukemic cell lines HL-60 and K562.
Laminin promotes the oxidative burst in human neutrophils via increased chemoattractant receptor expression.
Authors: Pike M C , Wicha M S , Yoon P , Mayo L , Boxer L A 
Published: December 2022

Abstract
The extracellular matrix component, laminin, enhances the chemotactic responsiveness of polymorphonuclear leukocytes (PMN) in vitro, and low doses of chemoattractant substances augment the expression of PMN cell surface receptors for laminin. This study determined whether laminin acts in concert with chemoattractants to activate PMN. Laminin (5 to 100 micrograms/ml) stimulated lysozyme release and superoxide production in response to the chemoattractant, FMLP by as much as 69%. These results could be explained by changes in cell surface chemoattractant receptor expression in that incubation of normal PMN with laminin (5 to 75 micrograms/ml) increased the binding of 19 nM FML[3H]P by 35 to 80%. This corresponded to as much as a 2.5-fold increase in the number of chemoattractant receptors/cells which had a lower average affinity. Laminin did not change the number or affinity of FML[3H]P receptors present on organelle-depleted PMN cytoplasts, and the laminin-induced increase in FML[3H]P receptors expressed on PMN from a patient with a specific granule deficiency was only 11 to 21% of that seen in normal PMN. These findings suggest that chemoattractants augment the expression of laminin receptors which mediate PMN attachment to basement membranes, followed by laminin-induced increases in the expression of cryptic chemoattractant receptors contained in intracellular granules, with resultant augmentation of the oxidative burst.
Developmental regulation of membrane and secretory Ig gamma 2b mRNA.
Authors: Brown S L , Morrison S L 
Published: December 2022

Abstract
To better understand the developmental regulation of membrane and secretory forms of Ig Heavy chain mRNA, mutations were made in a gamma 2b gene in vitro and assayed for their expression in cell lines representative of early and late stages of B cell development. Processing of the gamma 2b mRNA did not change with the amount of message produced, demonstrating that the production of predominantly secretory mRNA in plasma cells is not the consequence of increased message synthesis. The length of the intron between the secretory and membrane exons was found to affect the relative expression of secretory and membrane mRNA, but this effect was also observed in non-lymphoid cells, suggesting that the intron "gradient effect" does not identify the processing reaction which is regulated during B cell differentiation. Deletion of the signals for the splice from CH3 to the membrane exons resulted in the exclusive production of secretory mRNA irrespective of the developmental stage of the recipient cell, suggesting that this splice reaction plays a role in regulating these mRNA, and that competition between the two polyadenylation sites does not dictate the relative expression of the two forms of message. Appropriate ratios of the two forms were produced from a 2.3-kbp fragment of the gamma 2b gene containing the secretory cleavage and membrane splice signals in the context of a different transcription unit. These results suggest that the changes in the relative expression of secretory and membrane gamma 2b mRNA during B cell development are mediated by a competition between cleavage at the secretory polyadenylation and splicing from CH3 to the membrane exons.
Activation of eosinophils in cancer patients treated with IL-2 and IL-2-generated lymphokine-activated killer cells.
Authors: Silberstein D S , Schoof D D , Rodrick M L , Tai P C , Spry C J , David J R , Eberlein T J 
Published: December 2022

Abstract
Of 16 patients, a total of 13 who received IL-2 and autologous IL-2-generated lymphokine-activated killer LAK cells developed eosinophilia late during the course of treatment. To understand the direct or indirect effects of IL-2 on eosinophils, the physical and functional characteristics of the late-treatment eosinophils were compared to those of early-treatment and control eosinophils. Late-treatment eosinophils differed from early-treatment and control eosinophils in the following respects: they had somewhat reduced density, hypersegmented nuclei, eosinophil cationic protein converted from the storage form to the secretory form, and a greater than 200% increased ability to kill larvae of Schistosoma mansoni by an antibody-dependent mechanism (cytotoxic function). In vitro, IL-2 (1000 U/ml in medium as used to culture LAK cells) did not affect the cytotoxic function of eosinophils from cancer patients or from control subjects. However, LAK cell-conditioned medium enhanced the cytotoxic function of eosinophils from early-treatment cancer patients and from normal subjects by greater than 150%. Thus, eosinophils late in the course of IL-2/LAK cell treatment undergo physical changes and become functionally activated. The involvement of IL-2 in these changes is probably indirect, as an inducer of factors that enhance eosinophil function.
Requirements for suppressor cell activation. Role of accessory cells.
Authors: Kuchroo V K , Minami M , Diamond B , Dorf M E 
Published: December 2022

Abstract
In the 4-hydroxy-3-nitrophenyl acetyl (NP) suppressor system, third order suppressor cells (Ts3) subset of suppressor cells is generated after Ag priming, but, in order to express suppressor activity, these cells need to be further activated or triggered with a specific second order suppressor factor. By in vitro activation of Ts3-containing lymph node cells or a pTs3 hybridoma we now show that macrophages are also required for Ts3 activation. In addition, we demonstrate that IJ genetic restrictions control this activation process. Furthermore, we directly demonstrate Ts3 activation using cloned macrophage hybridoma cells. To further investigate the interactions between Ts3 cells and the accessory cells involved in their activation, we attempted to block the second order suppressor factor mediated activation of Ts3 cells with antibodies. The activation of Ts3 cells can be blocked by the addition of anti-IJ, anti-IJ idiotype or anti-NPb idiotype antibodies, but not by anti-CD8, anti-IA, or anti-IE antibodies. Anti-IJ mAb blocked Ts3 activation at the lymphocyte level whereas anti-IJ idiotype blocked activation at the accessory cell level. Finally we tested, whether these antibodies can also directly activate primed Ts3 cells. We demonstrate that cross-linked anti-IJ, anti-NPb and anti-CD3 antibodies can activate Ts3 cells. The results are discussed in terms of receptor-ligand structures on Ts and accessory cells which are required for the activation of Ts3 cells.
A monoclonal antibody raised to lipomodulin recognizes T suppressor factors in two independent hapten-specific suppressor networks.
Authors: Steele J K , Kuchroo V K , Kawasaki H , Jayaraman S , Iwata M , Ishizaka K , Dorf M E 
Published: December 2022

Abstract
Five different Ag-binding suppressor factors from two types of hapten-specific Ts cell hybridomas (TsF1 inducer and TsF3 effector factors) were bound by an anti-lipomodulin mAb (141-B9), that crossreacts with rodent glycosylation inhibition factor (GIF). The Ag-specific suppressor activity in these hybridoma supernatants was bound by anti-lipomodulin columns and could be recovered by elution at acid pH. Additional evidence for the expression of lipomodulin/GIF activity on these TsF molecules was demonstrated by the ability of the eluted fractions to inhibit the glycosylation of IgE-binding peptides during their biosynthesis. The same biologic activity is associated with GIF and lipomodulin. The relationship between TsF and lipomodulin/GIF was confirmed in a serologic assay, which showed that TsF1 and TsF3 molecules, whether purified over Ag, anti-IJ or anti-TsF columns, are recognized by the mAb. 141-B9. The combined results indicate that Ag-binding Ts factors share a common antigenic determinant with phospholipase inhibitory proteins such as lipomodulin and GIF. In addition, the demonstration of glycosylation regulatory activity carried on these TsF molecules suggests a possible mode for their bioactivity.