bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor.
Authors: Berkow R L , Wang D , Larrick J W , Dodson R W , Howard T H 
Published: December 2022

Abstract
Tumor necrosis factor (TNF) is a 17,000-Da protein which is produced by mononuclear cells upon exposure to endotoxin. Increases in adherence, phagocytosis, hydrogen peroxide release, and lysozyme secretion have been demonstrated after prolonged incubation of human neutrophils with TNF. In this study, the ability of highly purified recombinant human TNF to modulate neutrophil responses to soluble stimuli was evaluated. Tumor necrosis factor alone (0.1 to 10,000 units/ml) failed to induce neutrophil superoxide anion (O2-) production, granule release, or aggregation when incubated for up to 25 min at 37 degrees C. TNF did, however, stimulate a significant time-, dose-, and temperature-dependent increase in neutrophil F-actin content. Although exposure of neutrophils to TNF alone caused no superoxide anion production, it enhanced the O2- production in response to the chemotactic peptide, f-methionyl-leucyl-phenylalanine (FMLP) or the tumor promotor, phorbol myristate acetate, by as much as 278%. The enhancement was time-, dose-, and temperature-dependent and was due to a more rapid initial rate of O2- production. The TNF enhancement of FMLP-induced O2- production was blocked when an anti-TNF monoclonal antibody 241-1H11, is present during the preincubation period. TNF preincubation also enhanced FMLP-induced lysozyme release, but had no effect on aggregation and actin polymerization by FMLP. The kinetics of NADPH oxidase activation by arachidonic acid was unaltered by TNF. These results indicate that brief exposures to recombinant human TNF are able to enhance or prime the neutrophil oxidative burst in response to a second stimulus.
Inhibition of macrophage-mediated antigen presentation by hemolysin-producing Listeria monocytogenes.
Authors: Cluff C W , Ziegler H K 
Published: December 2022

Abstract
T lymphocytes and macrophages from Listeria-infected mice were used to evaluate the processing and presentation of live Listeria monocytogenes in vitro. Antigen presentation to T cells was quantitated by interleukin-2 production. In contrast to inert antigens such as heat-killed Listeria, live bacteria were processed and presented poorly. To evaluate the role of hemolysin (Hly), we used isogenic pairs of Hly+ and Hly- Listeria as antigens. In contrast to live Hly- bacteria, which were presented as well as heat-killed Listeria, live Hly+ bacteria were presented poorly. Hly+ bacteria also inhibited the presentation of heat-killed Listeria. This effect was apparent with as few as 10 bacteria/macrophage and was not due to loss of macrophage viability or decreased Ia expression after exposure to the live bacteria. With respect to murine listeriosis, the LD50 values for the Hly- strains were at least 1000 times higher than those for the Hly+ strains. These results suggest that the ability of Hly+ bacteria to inhibit antigen processing and presentation may be an important determining factor in Listeria infection and immunity.
A transgenic class I antigen is recognized as self and functions as a restriction element.
Authors: Yoshioka T , Bieberich C , Scangos G , Jay G 
Published: December 2022

Abstract
The function of a transgenic Dd class I molecule in the induction of immunologic tolerance to major histocompatibility complex antigens and in directing major histocompatibility complex restriction in C57BL/6 mice were investigated. All of the transgenic Dd mouse strains were found to be tolerant for the Dd antigen. Spleen cells from transgenic mice were immunocompetent but consistently failed to generate an anti-Dd cytotoxic T lymphocyte response in vitro, and skin grafts between transgenic Dd mice were not rejected. These data suggests that the Dd antigen was recognized as a self molecule. In addition, the transgenic Dd mice generated antigen-specific Dd-restricted cytotoxic T lymphocyte, indicating that the Dd antigen also functioned as a restriction element for antigen recognition. These observations demonstrate the usefulness of the transgenic mouse system for studying class I antigen expression and function.
DNA sequence analysis of the C3H H-2Kk and H-2Dk loci. Evolutionary relationships to H-2 genes from four other mouse strains.
Authors: Watts S , Vogel J M , Harriman W D , Itoh T , Stauss H J , Goodenow R S 
Published: December 2022

Abstract
We generated nucleotide sequences for H-2Kk and H-2Dk from the C3H mouse, as well as for a genomic clone of H-2Db, in order to conduct an evolutionary analysis of the H-2 genes from three haplotypes, k, d, and b. H-2Kk from both the C3H and AKR strains, H-2Kd, H-2Kb, H-2Dk, H-2Ld, H-2Dd, H-2Db, and H-2Dp DNA sequences were aligned, and the alignments used to construct phylogenetic trees inferring the evolutionary relationships among the nine genes by two independent methods. Both approaches yielded trees with similar topologies. In addition, the sequence alignments revealed patterns of nucleotide substitutions which implicate both point mutation and recombination in the divergence of the H-2 genes. Future considerations for evolutionary analysis of class I genes are discussed.
Lymphoma models for B cell activation and tolerance. VI. Reversal of anti-Ig-mediated negative signaling by T cell-derived lymphokines.
Authors: Scott D W , O'Garra A , Warren D , Klaus G G 
Published: December 2022

Abstract
We have recently described three "immature" B cell lymphomas which are exquisitely sensitive to growth inhibition by anti-Ig reagents and may serve as models for tolerance induction in normal B cells. These cells are inhibited from cell cycle progression into S after receiving a negative signal in early G1. In this paper, we demonstrate that the growth inhibition by anti-Ig can be prevented and reversed by the addition of supernatants from T cell lines. One such line, called Tova, produces factors which restore normal levels of DNA synthesis in the presence of concentrations of anti-Fab or anti-kappa immunoglobulins which cause up to a 90% inhibition of thymidine incorporation in a 2- to 3-day culture period. This factor is at least partially effective when added up to 24 hr after anti-Ig to unsynchronized lymphoma cells and it does not alter the growth of control cultures. Studies using synchronized lymphoma cells indicated that the T cell factor permitted cycle progression into S when added during the early G1 exposure to anti-kappa and was less effective when added late in G1. Preliminary characterization suggests that both B cell growth factor II (interleukin 5) and B cell stimulatory factor 1 (interleukin 4) have additive activity in this system, although another unidentified lymphokine may also be involved. The relevance of T cell reversal of Ig receptor-mediated negative signaling to neonatal B cell tolerance is emphasized.
Stepwise activation of T cells. Role of the calcium ionophore A23187.
Authors: Geller R L , Gromo G , Inverardi L , Ferrero E , Bach F H 
Published: December 2022

Abstract
The calcium ionophore A23187, at a concentration of 1 microgram/ml, is able to stimulate proliferation of freshly isolated peripheral blood lymphocytes, CD4+-enriched cells, or CD8+-enriched cells as measured by [3H]thymidine incorporation. This proliferation is accompanied by an increase in interleukin 2 (IL-2) receptor expression but not by a detectable up-regulation in (IL-2) production or the development of cytotoxicity. Proliferation can be blocked by anti-CD3, CD4, or CD8 monoclonal antibodies, but not by anti-Tac. If CD8+-enriched cells are activated for 3 days with A23187 and the blasts present on day 3 are sorted and returned to culture, they rapidly develop cytolytic activity in the presence of recombinant IL-2 but not recombinant interferon-gamma. CD4+ enriched cells, after activation with A23187, do not become cytotoxic in the presence of either recombinant IL-2 or recombinant interferon-gamma. These findings permit study of the stepwise maturation of T cells in this alternative pathway by using "minimal signals" that do not, by themselves and as used in these studies, stimulate precursor Tc to mature to full effector cytotoxic function. These findings are consistent with the model that A23187 drives T cells only part way along a pathway of maturation and that an additional second signal must be given to effect maturation of cytotoxic status.
Phosphorylation of CD4 and CD8 molecules following T cell triggering.
Authors: Blue M L , Hafler D A , Craig K A , Levine H , Schlossman S F 
Published: December 2022

Abstract
CD4 and CD8 molecules have been implicated in the regulation of T cell activation. In the present study, CD4 and CD8 were modified by increased phosphorylation when T cell clones or T cells were either exposed to phorbol-12-myristate- 13-acetate or were triggered via the CD3-T cell receptor complex. Activation of T cells through the CD2 sheep erythrocyte binding protein, using anti-T11(2) and -T11(3) antibodies, also resulted in CD4 and CD8 phosphorylation. These findings suggest that signals derived from two different receptor pathways can converge and result in similar molecular modifications of CD4 and CD8. Furthermore, phorbol myristate acetate treatment or activation via the CD2 pathway induced phosphorylation of the CD4 and CD8 molecules of thymocytes, suggesting that these molecules may be functional in thymus. Together, our findings indicate that CD4 and CD8 phosphorylation is a consequence of T cell triggering, and suggest that CD4 and CD8 phosphorylation may represent a molecular signaling mechanism among the CD3-T cell receptor complex, CD2, CD4, and CD8.
Generation of antisuppressor T cells for alloreactive cytotoxic T lymphocytes.
Authors: Ting C C , Hargrove M E 
Published: December 2022

Abstract
This study demonstrated that antisuppressor T cells (TAS) were generated in allogeneic mixed lymphocyte culture (MLC) when supplemented with a conditioned medium containing T cell differentiation factor (CM-TCDF). CM-TCDF was shown to efficiently restore the alloreactive cytotoxic T lymphocytes (CTL) response in accessory cell-depleted MLC. CM-TCDF could also sustain the growth and cytotoxic activity of bulk-cultured CTL. In contrast, cloned CTL only required interleukin 2 to maintain their growth and cytotoxic activity. These findings suggested that bulk-cultured MLC might contain different populations of immunoregulatory cells in addition to CTL effectors. These immunoregulatory cells provide "on" or "off" signals to turn on or turn off the lytic machinery of CTL. The suppressor T cells (Ts) generated in MLC might provide the "off" signal to CTL that resulted in the termination of their cytotoxic activity after 7 days of culturing. When CM-TCDF was supplemented in MLC, we found that TAS were generated. TAS could efficiently abrogate the suppressor activity of anti-allo-TS, but they had no effect on the anti-self veto cell activity. Both the TAS and TS activities were allospecific. The precursors and effectors of TAS were both found to be L3T4+ cells, whereas the TS effectors were Lyt-2+ cells. Generation of TAS was completely blocked by alpha L3T4 antibody and was partially blocked by alpha Thy-1 antibody. In contrast, alpha Lyt-2 antibody or antibodies against class II major histocompatibility complex framework determinants had no effect on TAS generation. Therefore, TAS were different from L3T4+ T helper cells that were induced in the context of recognizing class II major histocompatibility complex determinants. TAS might represent a separate set of immunoregulatory cells that provide an "off" signal to the TS, which allowed the lytic machinery of the CTL to remain active and, thus, to maintain their cytotoxic activity for a prolonged period of time.
L3T4+ cytotoxic T lymphocytes specific for class I H-2 antigens are activated in primary mixed lymphocyte reactions.
Authors: Macphail S , Stutman O 
Published: December 2022

Abstract
Thy-1+, L3T4+, Ly-2- cytotoxic lymphocytes (CTL) are generated in a primary anti-H-2d mixed lymphocyte reaction, by using responders depleted of Ly-2+ cells. In addition to expressing the L3T4 marker, as detected by anti-L3T4 antibody and complement-mediated elimination, the L3T4+ CTL are inhibited by L3T4 antibody. The observation of these L3T4+ CTL in cells recovered from primary mixed lymphocyte reactions confirms the previous reports. However it is demonstrated for the first time that a subpopulation of these are class I-specific by their specific inhibition with an antiserum to class I antigens. The class I specificity of the CTL was further shown by their ability to kill class II antigen negative P815 tumor cells. The lysis of this target cell by L3T4+ CTL was also specifically blocked by the class I antiserum. The data is consistent with the presence also of a class II-specific population of L3T4+ cytotoxic cells. The fact that a level of L3T4+ cell-mediated cytotoxic activity comparable to Ly-2+ cytolytic activity is generated in a primary mixed lymphocyte response, even though the precursor frequency of L3T4+ killer cells is 10 times lower than for Ly-2+ killers, is suggestive of their physiologic significance. It was also shown that the activation of these cells is not dependent on the presence of xenogeneic serum components or exogenous helper or mitogenic factors in the culture medium. The findings provide further evidence against both the phenotype-function and phenotype-major histocompatibility complex antigen specificity models of T cell diversity.
Defective thymocyte maturation in horses with severe combined immunodeficiency.
Authors: Wyatt C R , Magnuson N S , Perryman L E 
Published: December 2022

Abstract
Six monoclonal antibodies, designated EqT2, EqT3, EqT6, EqT7, EqT12, and EqT13, which identify T lymphocyte antigens present at different stages of T cell maturation were used to examine T lymphocyte development in foals with severe combined immunodeficiency (SCID). Flow microfluorimetry demonstrated the presence of EqT12+ and EqT13+ prothymocytes and a few phenotypically mature EqT2+ and EqT3+ thymocytes within the thymic remnants of SCID foals. However, very few EqT6+ and EqT7+ resident cortical thymocytes were detected. The near absence of EqT6+ and EqT7+ cortical thymocytes was confirmed by immunofluorescence analysis of thymic tissue from SCID foals. Those cells present were larger than normal cortical thymocytes. Furthermore, their activities of adenosine deaminase, adenosine monophosphate-deaminase, and 5' nucleotidase differed from those of normal cortical thymocytes. The combined evidence of monoclonal antibody analysis, size parameters, and purine enzyme activities demonstrate the near absence of cortical thymocytes in horses with this genetically defined immunodeficiency disorder.
The augmentation of surface Ly-6A/E molecules in activated T cells is mediated by endogenous interferon-gamma.
Authors: Dumont F J , Boltz R C 
Published: December 2022

Abstract
The murine Ly-6A.2 and Ly-6E.1 antigens, which can transduce triggering signals in T cells, have been shown to become highly expressed after mitogenic stimulation. It has recently been found that enhanced expression of Ly-6A/E antigens is also induced by interferon-gamma (IFN-gamma) in resting T cells. Here, the possibility is investigated that Ly-6A/E induction on activated T cells may be due to the IFN-gamma known to be secreted by these cells. A potent neutralizing anti-IFN-gamma monoclonal antibody (mAb) (H-22.10) was used. This mAb was found to abrogate the augmentation of Ly-6A/E antigens produced in resting T cells by supernatants from T cells stimulated with concanavalin A. When added directly into cultures of T cells stimulated with concanavalin A or by the combination of ionomycin with the protein kinase C activator phorbol myristate acetate (PMA), the H-22.10 mAb inhibited Ly-6A/E enhancement without affecting the blastogenesis or the emergence of interleukin 2 receptors and transferrin receptors. Such a selective effect of the anti-IFN-gamma mAb indicated that IFN-gamma is involved in the up-regulation of Ly-6A/E antigens during T cell activation. In determining whether other activation signals, in addition to IFN-gamma receptor occupancy, may contribute to Ly-6A/E enhancement, it was found that suboptimal stimulation of BALB/c T cells provided by a 3-hr pulse with ionomycin plus PMA or by culture with PMA alone potentiated by about twofold the increase of Ly-6E.1 induced by exogenous IFN-gamma. Therefore, Ly-6A/E augmentation in activated T cells reflects primarily an action of endogenous IFN-gamma that is amplified (in BALB/c mice) by a protein kinase C-dependent step.
Molecular cloning and expression of hybridoma growth factor in Escherichia coli.
Authors: Brakenhoff J P , de Groot E R , Evers R F , Pannekoek H , Aarden L A 
Published: December 2022

Abstract
Human monocytes produce a factor that supports the growth of B lymphocyte hybridoma cells, termed hybridoma growth factor (HGF). By using expression cloning in Escherichia coli of complementary DNA derived from human monocyte-poly(A+) RNA, we selected seven clones producing HGF activity as measured in a bioassay, based on the induction of proliferation of the HGF-dependent B cell hybridoma B9. Sequence analysis of the cDNA revealed that HGF is identical with interferon-beta 2, 26,000 protein, and B cell stimulatory factor-2. One of the active clones contained a cDNA that encoded a recombinant product lacking the 28-amino acid long signal peptide and the first 15 amino acids of the mature protein. Antibodies against the recombinant HGF inhibited the biologic activity of recombinant HGF as well as of monocyte-derived HGF.
The effects of N-3 polyunsaturated fatty acids on the generation of platelet-activating factor-acether by human monocytes.
Authors: Sperling R I , Robin J L , Kylander K A , Lee T H , Lewis R A , Austen K F 
Published: December 2022

Abstract
Human leukocytes generate platelet-activating factor (PAF-acether), a lipid mediator of inflammation, from membrane alkyl phospholipids through the release of arachidonic acid or other fatty acids at the 2-position and subsequent acetylation. Because it was previously demonstrated that fish oil fatty acids suppress human leukocyte arachidonic acid release and metabolism, separate experiments were conducted to investigate the effects of dietary fish oil supplementation and in vitro incubation with fish oil fatty acids on calcium ionophore-stimulated PAF-acether generation in human monocytes. In subjects on their regular diets, a 4-hr incubation of monocyte monolayers with an optimally effective concentration of arachidonic acid of 1 micrograms/ml resulted in a 64% increase of calcium ionophore-induced net PAF-acether generation from 7.75 +/- 0.78 ng/10(6) cells for untreated monolayers to 12.70 +/- 1.21 ng/10(6) cells (mean +/- SEM). Treatment of monolayers with eicosapentaenoic acid (EPA) at the optimal concentration of 1 micrograms/ml decreased net PAF-acether generation by 28%. However, treatment of monocyte monolayers with docosahexaenoic acid did not appreciably affect net PAF-acether generation. The changes in PAF-acether release with each fatty acid added in vitro paralleled those in total PAF-acether generation; the percentage PAF-acether release remained unaffected. Three weeks of dietary supplementation with 18 g MaxEPA daily, providing 3.2 g EPA did not affect the PAF-acether generation of calcium ionophore-stimulated human monocyte monolayers. However, 6 weeks of dietary supplementation resulted in a 47% decrease of net total PAF-acether generation and a concomitant 59% decline in net PAF-acether release; the percentage release of PAF-acether was not affected. Thus, whether added to the diet or introduced in vitro, fish oil-derived fatty acids suppress PAF-acether generation by human monocyte monolayers.
Tolerance induction in mice by conjugates of monoclonal immunoglobulins and monomethoxypolyethylene glycol. Transfer of tolerance by T cells and by T cell extracts.
Authors: Wilkinson I , Jackson C J , Lang G M , Holford-Strevens V , Sehon A H 
Published: December 2022

Abstract
The specific tolerance induced in mice by conjugates of human monoclonal IgG (HIgG) with monomethoxypolyethylene glycol (mPEG) was transferred to normal mice by spleen cells or a surface immunoglobulin negative (sIg-) Lyt-2+ subpopulation of these cells. Although transferable tolerance was demonstrable 6 to 14 days after treatment of the cell donors with tolerogen, the state of tolerance persisted in the treated mice for at least 43 days. Moreover, an extract prepared by freezing and thawing of the sIg- spleen cells obtained from mice 6 days after treatment with HIgG(mPEG)20 was capable of reducing (greater than 85%) the immune response of normal mice to heat aggregated HIgG. On the basis of these results, it is suggested that similar tolerogenic mPEG derivatives of xenogeneic monoclonal immunoglobulins (XIg) may prove to be useful therapeutic agents in man when administered before treatment with the unmodified XIg.
Identification of human anti-DNA, anti-RNP, anti-SM, and anti-SS-A serum antibodies bearing the cross-reactive 16/6 idiotype.
Authors: Kaburaki J , Stollar B D 
Published: December 2022

Abstract
The human idiotype 16/6, characteristic of lupus-derived anti-DNA autoantibodies, was detected in sera of Japanese patients with autoimmune diseases. The 16/6-positive sera were from patients with active SLE and, in one case, a scleroderma-polymyositis overlap syndrome; all contained anti-ssDNA antibody. Affinity chromatography was used to isolate 16/6-bearing Ig from sera of seven patients having anti-DNA and other autoantibodies. In a preliminary step, rheumatoid factors and nonspecific binding were removed by four passes of the serum through a column of immobilized normal rabbit gamma-globulin. The absorbed sera were then applied to a column of immobilized specific rabbit anti-16/6 globulin. This combined procedure depleted anti-ssDNA activity selectively. From 44 to 60% of total Ig but only 6 to 25% of anti-ssDNA activity was recovered in the material that passed through both columns. Approximately 40% of the anti-RNP/Sm and anti-SS-A/SS-B activities were recovered, reflecting a lesser degree of selective depletion of these antibodies. The specific eluate from the anti-idiotype column contained more IgG than IgM; anti-DNA activity; anti-RNP, anti-Sm, or anti-SS-A activity. Soluble DNA inhibited the binding of one eluate to RNP/Sm but not of another eluate to SS-A/SS-B. The results confirm that the genes encoding the 16/6 idiotype are widely represented in ethnically different human populations, and indicate that 16/6-bearing Ig may bind to other autoantigens as well as to DNA.