bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role and effect of IL-2 in experimental visceral leishmaniasis.
Authors: Murray H W , Miralles G D , Stoeckle M Y , McDermott D F 
Published: January 2023

Abstract
In experimental visceral leishmaniasis, acquired resistance is T cell-dependent, involves IFN-gamma-activated macrophages, and is expressed in the tissues by granuloma formation. Resistance also correlates with Ag-stimulated IL-2 secretion; therefore, Leishmania donovani-infected BALB/c mice were treated with anti-IL-2 mAb or rIL-2 to determine the host defense effect of IL-2. In control mice, intracellular hepatic infection peaked at 2 wk and then declined coincident with granuloma development. In contrast, liver parasite burdens in anti-IL-2-treated mice continued to increase until after 4 wk, at which time mature granuloma formation was inhibited. Treatment of mice with continuously administered IL-2 reduced liver burdens by &gt; 50% and led to marked accumulation of granuloma mononuclear cells. The IL-2-responsive mechanism was T cell-dependent and required both L3T4+ and Lyt-2+ cells. IL-2 enhanced IFN-gamma mRNA expression in vivo and was required for IFN-gamma secretion in vitro, and anti-IFN-gamma mAb administration abolished the antimicrobial effect of exogenous IL-2. These results: 1) identify the activity of endogenous IL-2 in both antileishmanial resistance and granuloma formation; 2) demonstrate that exogenous IL-2 can enhance the granulomatous tissue reaction; and 3) indicate that IL-2 treatment stimulates intracellular antimicrobial activity largely via the induction of IFN-gamma.
Expression of decay-accelerating factor (CD55) of the complement system on human spermatozoa.
Authors: Cervoni F , Oglesby T J , Fénichel P , Dohr G , Rossi B , Atkinson J P , Hsi B L 
Published: January 2023

Abstract
Human spermatozoa were analyzed for their expression of decay-accelerating factor (DAF, CD55), a glycolipid-anchored regulatory protein of the C casade. Morphologic data showed that DAF was localized at the acrosomal region of the sperm head. Analysis with anti-DAF antibody-immunoprecipitated proteins of acrosome-reached spermatozoa revealed a 44- to 54-kDa protein. Carbohydrate analysis of sperm DAF indicated that it contains nonsialated N- and O-linked sugars. The absence of mature oligosaccharides on this protein appears to account for the difference in molecular mass between sperm DAF and the 70-kDa DAF expressed on other human tissues. Sperm DAF reinserted into sheep E and inhibited C-mediated lysis. This effect was reversed by mAb, which block DAF function. These results indicate that sperm DAF also possesses a glycolipid anchor. The expression of DAF on acrosome-reacted spermatozoa suggests that it may act concomitantly with other C regulators such as membrane cofactor protein to modulate the activation of C in the immunocompetent female genital tract and protect acrosome-reacted spermatozoa from C-mediated attack.
Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6.
Authors: McGee D W , Beagley K W , Aicher W K , McGhee J R 
Published: January 2023

Abstract
Intestinal epithelial cells are a potentially important source for a number of cytokines that may modulate the immune response at the intestinal mucosa. We have recently begun to study the mechanisms that regulate IL-6 production by intestinal epithelial cells using the nontransformed crypt-like rat intestinal epithelial cell line IEC-6 as a model. Culture of the IEC-6 cells with human rIL-1 beta resulted in an enhanced secretion of IL-6 by the cells. RT-PCR analysis of IL-1 beta-treated cells showed an enhanced level of IL-6 mRNA at 4 h, suggesting that IL-1 beta enhanced IL-6 gene expression. In a previous study, transforming growth factor-beta (TGF-beta 1) was also found to enhance IL-6 secretion by the IEC-6 cells and because both IL-1 beta and TGF-beta may be present in inflamed mucosal tissue, the effect of adding both cytokines together was next investigated. Culture of the IEC-6 cells with both TGF-beta 1 and IL-1 beta resulted in a synergistic enhancement of IL-6 secretion that was seen even at high levels of both TGF-beta and IL-1 beta. IL-6 mRNA levels from cells treated with both TGF-beta 1 and IL-1 beta were also determined to be enhanced when compared to that of cells treated with IL-1 beta or TGF-beta 1 only, as determined by RT-PCR analysis. Pretreatment of the IEC-6 cells with TGF-beta 1 for 2 or 3 days before addition of the IL-1 beta induced the IEC-6 cells to differentiate and become more sensitive to stimulation by IL-1 beta. Subsequent experiments determined that TGF-beta enhanced the capacity of the IEC-6 cells to bind labeled IL-1 beta indicating that TGF-beta may have enhanced the expression of IL-1 receptors on the cells. These results suggest that the intestinal epithelial cell may represent an important source of IL-6 in inflammatory responses at the intestinal mucosa and that TGF-beta could potentiate this function.
Production of minor lymphocyte stimulatory-1a antigen from activated CD4+ or CD8+ T cells.
Authors: Arase-Fukushi N , Arase H , Ogasawara K , Good R A , Onoé K 
Published: January 2023

Abstract
Minor lymphocyte stimulatory (Mls) Ag are super Ag that stimulate a high proportion of T cells of a specific TCR V beta family. One of the super Ag, Mls-1a, which is recognized mainly by TCR V beta 6+ and V beta 8.1+ T cells, has recently been linked to the response to product of the open reading frame in 3'-long terminal repeat of endogenous mammary tumor virus, MTV-7. It is quite certain that B cells are able to produce and also to present the Mls-1a Ag. However, it remains to be determined whether other cell types, especially T cells, produce Mls-1a Ag. In this study using highly purified T cell subpopulations, capacity to produce Mls-1a Ag was analyzed by calculating the proportion of Mls-1a reactive V beta 6+ or V beta 8.1+ T cells in responding cell populations. We found that nonstimulated CD8+ T cells produced a low amount of Mls-1a Ag, and the capacity to do so was considerably increased by stimulation with immobilized anti-TCR mAb. By contrast, nonstimulated CD4+ T cells did not produce Mls-1a Ag at all. Even when CD4+ T cells were activated via TCR signaling with immobilized anti-TCR mAb, CD4+ T cells did not produce Mls-1a Ag. However, CD4+ T cells primed with conventional Ag in vivo produced Mls-1a Ag on restimulation with that specific Ag in vitro. These findings indicate that not only CD8+ T cells but also CD4+ T cells can produce Mls-1a Ag on appropriate stimulation, although different mechanisms for Mls-1a production may operate between the CD4+ and CD8+ T cells.
The expression of CD4 by T cell precursors resident in both the thymus and the bone marrow.
Authors: Chervenak R , Dempsey D , Soloff R , Wolcott R M , Jennings S R 
Published: January 2023

Abstract
A very small fraction of thymocytes has recently been identified that expresses low levels of CD4 in the absence of CD8, CD3, or a TCR. These CD4lo thymocytes appear to be the precursors of the early CD4-CD8-CD3- thymic subset and contain most of the T cell progenitor activity found within the thymus. Here, we examined adult bone marrow for the presence of a similar population of cells and found that 0.5% to 3.5% of C58/J bone marrow cells express low, but detectable levels of CD4 (CD4lo) at the cell surface in the absence of CD3. These CD4lo bone marrow cells display pre-T cell activity, in that they are able to repopulate the thymus of irradiated recipient mice after intrathymic transfer. Moreover, we found that most of pre-T cell activity found in the bone marrow is contained within the CD4lo expressing subset of marrow cells. Although the CD4lo cells found in both the thymus and bone marrow display pre-T cell activity, the CD4lo cells from these two sites showed pronounced differences with respect to their ability to respond to specific cytokine stimulation in vitro. Bone marrow-resident CD4lo cells proliferated in response to both IL-3 and mast cell growth factor in vitro, whereas CD4lo cells isolated from the thymus did not. Furthermore, CD4lo bone marrow cells, grown in media containing IL-3 and mast cell growth factor, retained their pre-T cell activity, indicating that CD4lo cells with pre-T cell capabilities were among the IL-3 and mast cell growth factor-responsive cells. These data suggest that although pre-T cells in bone marrow share the CD4lo phenotype with their intrathymic counterparts, they may be fundamentally different with respect to the environmental factors that control their growth.
TGF-beta is a bidirectional modulator of cytokine receptor expression on murine bone marrow cells. Differential effects of TGF-beta 1 and TGF-beta 3.
Authors: Jacobsen S E , Ruscetti F W , Roberts A B , Keller J R 
Published: January 2023

Abstract
Transforming growth factor beta (TGF-beta), an immunomodulator, has inhibitory as well as stimulatory effects on bone marrow cells. In this study, we demonstrate that TGF-beta 1 also is a bidirectional modulator of CSF receptor expression on murine bone marrow cells. TGF-beta 1 up-regulated granulocyte-macrophage (GM)-CSF receptor expression in a time- and dose-dependent manner, with a maximum up-regulation of 64% by 48 h at 20 ng/ml. In contrast, TGF-beta 1 down-modulated IL-3 and CSF-1 receptor expression by 54 and 55%, respectively, by 24 h. TGF-beta 1 did not affect G-CSF receptor expression, in agreement with its inability to affect G-CSF-induced proliferation. The CSF receptor modulation induced by TGF-beta 1 preceded its effects on CSF-stimulated proliferation. The effects of TGF-beta on CSF receptor expression were isoform dependent, thus TGF-beta 3 was a 10-fold more potent inhibitor of both IL-3-induced colony formation and IL-3 receptor expression than TGF-beta 1, whereas TGF-beta 1 was a more potent stimulator of GM-CSF-stimulated colonies and GM-CSF receptor expression than TGF-beta 3. Therefore, the ability of TGF-beta to modulate the CSF receptor density/cell and/or the actual number of progenitors expressing CSF receptors directly correlates with the multifunctional effects of TGF-beta in hematopoiesis.
Stimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor.
Authors: Tartaglia L A , Goeddel D V , Reynolds C , Figari I S , Weber R F , Fendly B M , Palladino M A 
Published: January 2023

Abstract
TNF-alpha can enhance the proliferation of human thymocytes stimulated by the comitogen Con A. To determine which of the two different TNF receptors is responsible for signaling this cellular response, we investigated the proliferation of human thymocytes in response to agonistic antibodies specific for the two TNF receptor types. In contrast to previously examined TNF activities in human cells, thymocyte proliferation was stimulated in response to rabbit polyclonal antibodies directed against the 75-kDa TNF receptor (TNF-R2), but not those directed against the 55-kDa TNF receptor (TNF-R1). Lymphotoxin (TNF-beta) was also shown to stimulate human thymocyte proliferation, demonstrating that TNF-beta can initiate a biologic response that is mediated by TNF-R2. TNF-R2-mediated T-cell proliferation was not restricted to the immature T cells within the thymus, as the anti-TNF-R2 antibodies also stimulated the proliferation of peripheral T cells. As a first step toward identifying a specific agonist of TNF-R2 with therapeutic potential, 10 anti-TNF-R2 mAb were examined for potential agonist activity. Nine of these significantly stimulated human thymocyte proliferation with maximal responses ranging from twofold to significantly greater than that obtained with TNF-alpha by itself.
Construction of a human Ig combinatorial library from genomic V segments and synthetic CDR3 fragments.
Authors: Akamatsu Y , Cole M S , Tso J Y , Tsurushita N 
Published: January 2023

Abstract
A naive combinatorial Ig library was constructed from semi-synthetic V genes consisting of human genomic V segments and synthetic CDR3 fragments. VH and V kappa segments were amplified from human genomic DNA by polymerase chain reaction using V subgroup-specific primers. The amplified VH and V kappa segments were combined with synthetic oligonucleotides containing a J region and CDR3 with amino acid sequence variations, resulting in complete V genes. These V genes were cloned into a phagemid expression vector in a single-chain form fused to the carboxyl-terminus of the M13 minor coat protein III. Phagemid particles displaying the single chain hybrid proteins on their surface were screened with Con A as Ag. Several clones showing specific binding to Con A were obtained after four rounds of selection and were further analyzed for their binding properties and DNA sequences. This method provides a novel way to create a naive combinatorial library without using mRNA from B lymphocytes as template. The method should be useful to isolate human antibodies that react with self-Ag.
Purification and characterization of chimeric human IgA1 and IgA2 expressed in COS and Chinese hamster ovary cells.
Authors: Morton H C , Atkin J D , Owens R J , Woof J M 
Published: January 2023

Abstract
Ag-specific chimeric human IgA molecules, of the two human subclasses, IgA1 and IgA2, have been expressed in two mammalian cell systems. Analysis of the secreted IgA molecules, purified in milligram quantities from stable Chinese hamster ovary transfectants by Ag affinity chromatography, has allowed a direct comparison of the biologic properties of the two subclasses. HPLC gel filtration analysis revealed that in both subclasses, the IgA molecules associate predominantly into dimers. The monomer units are presumed to interact noncovalently, inasmuch as no dimers are evident when the antibodies are subjected to SDS-PAGE. The recombinant antibodies are glycosylated, inasmuch as a lectin blotting procedure revealed that the H chains of both subclasses are recognized by Con A. When subjected to digestion by preparations of IgA1-specific proteases secreted by two pathogenic streptococcal strains, Streptococcus sanguis and Streptococcus oralis, the recombinant IgA molecules behave just as their natural equivalents. Thus, only the chimeric IgA1 molecule is cleaved, with the IgA2 remaining intact. In terms of interaction with natural effector molecules, both recombinant IgA isotypes were shown to interact with Fc alpha receptors on calcitriol-stimulated HL-60 cells with similar affinity, but neither antibody was found to interact with human C1q. The expression system described readily permits manipulation of the human IgA genes, which should lead to a fuller molecular understanding of how this important antibody mediates its function.
Killing of Staphylococcus aureus by tumor necrosis factor-alpha-activated neutrophils. The role of serum opsonins, integrin receptors, respiratory burst, and degranulation.
Authors: Ferrante A , Martin A J , Bates E J , Goh D H , Harvey D P , Parsons D , Rathjen D A , Russ G , Dayer J M 
Published: January 2023

Abstract
We have examined the effects of TNF priming on the killing of Staphylococcus aureus by human neutrophils. In the absence of serum opsonins, neutrophils failed to kill S. aureus, and TNF priming did not induce the cells to become bactericidal. Normal human serum, containing complement activity, promoted the killing of the bacteria by neutrophils. Pretreatment of neutrophils for 30 min with TNF significantly enhanced their bactericidal activity. The effects of TNF on neutrophil bactericidal activity was dependent on serum concentration and the degree of enhancement induced increased up to a concentration of 1%. The kinetics of bacterial killing showed that TNF-only enhanced the initial rate of killing, over the first 30 min. Little killing of bacteria occurred in the presence of complement-inactivated serum, and TNF did not stimulate this killing. These results suggest that TNF enhances the neutrophil complement-dependent killing of S. aureus. TNF increased the expression of CR3 (CD11b/CD18) and CR4 (P150, 95; CD11c/CD18) adhesion receptors but not LFA-1 (CD11a/CD18); and mAb against the alpha-chain of either CR3 or CR4 but not LFA-1 prevented the enhancing effects of TNF on the neutrophil bactericidal activity.
Role of kinins in the vascular extravasation evoked by antigen and mediated by tachykinins in guinea pig trachea.
Authors: Bertrand C , Nadel J A , Yamawaki I , Geppetti P 
Published: January 2023

Abstract
Tachykinins released from sensory nerves mediate, at least in part, the plasma extravasation induced by allergen challenge to the airways of sensitized guinea pigs. We investigated the role of kinins in this activation of sensory nerves. We found that the increase in Evans blue dye extravasation evoked by aerosol of bradykinin (100 microM, 2 min) in the presence of phosphoramidon (2.5 mg/kg, i.v.) was abolished completely by the selective B2 bradykinin antagonist, HOE 140 (0.1 mumol/kg, i.v.), and was inhibited (60%) by the selective NK1 tachykinin receptor antagonist, CP-96,345 (2 mumol/kg, i.v.). Plasma extravasation evoked by aerosolized substance P (10 microM/kg, 2 min) in presence of phosphoramidon was abolished by CP-96,345, but was not affected by HOE 140. The extravasation of the Evans blue dye evoked by OVA (5%, 2 min) in sensitized guinea pigs was reduced by HOE 140 (45%) when the animals were perfused after 5 min and by 39% when perfusion was performed at 10 min. In the presence of phosphoramidon, the response to OVA at 10 min was reduced by 57% by HOE 140 and by 72% by CP-96,345. The combination of CP-96,345 and HOE 140 did not further increase the inhibition obtained with CP-96,345 alone. The results provide evidence that the activation of sensory nerves that contribute to Ag-evoked plasma extravasation is due to kinin release. The contribution of this cascade of events may be exaggerated in pathophysiologic conditions in which neutral endopeptidase is down-regulated.
The effects of stem cell factor on the ultrastructure of Fc epsilon RI+ cells developing in IL-3-dependent murine bone marrow-derived cell cultures.
Authors: Rottem M , Goff J P , Albert J P , Metcalfe D D 
Published: January 2023

Abstract
Stem cell factor (SCF) is known to alter the proteoglycans, proteases, and cytokines synthesized by mast cells and to activate basophils. To determine whether SCF could also effect the ultrastructural characteristics of basophils and mast cells, we examined the ultrastructure of these Fc epsilon RI+ cells over 42 days in IL-3-dependent murine bone marrow-derived cell cultures in the presence or absence of SCF. Initial experiments revealed that the addition of SCF to IL-3-dependent cells enhanced their proliferative rate without influencing the percentage of Fc epsilon RI+ or metachromatic cells. We next isolated the Fc epsilon RI+ cells using flow cytometry. Light microscopy of these cells revealed mixed cultures of both immature and mature mast cells and basophils with mature mast cells predominating by 3 wk. One hundred to 150 Fc epsilon RI+ cells were then photographed by electron microscopy at 3, 10, 21, and in some cases, 42 days of culture, and the ultrastructure of each cells was evaluated by morphometry. Each cell was scored as a mast cell or basophil using standard criteria. Analysis of this data revealed that SCF in the presence of IL-3 promoted the development of mast cells, although a significant number of basophils were noted at day 21 but were absent by day 42. When bone marrow cells cultured in IL-3 + SCF were compared with cells cultured in IL-3 alone, a significant decrease in cell and nuclear size and granule number and size was noted in both mast cells and basophils cultured in IL-3 + SCF, and basophils and mast cells under these conditions most resemble their in vivo counterparts. Thus, SCF in the presence of IL-3 increases the ratio of mast cells to basophils and alters the ultrastructural characteristics of mast cells and basophils toward a more mature phenotype.
Study of natural lipocortin I. A potent mediator for macrophage-mediated immunosuppression in tumor-bearing mice.
Authors: Sakata T , Iwagami S , Tsuruta Y , Suzuki S , Suzuki R 
Published: January 2023

Abstract
We previously reported a possible role of lipocortin I secreted from Mac-1+, -2+ macrophages in immunosuppression in tumor-bearing mice. In this study, we purified natural lipocortin I from the spleens of tumor-bearing mice and compared its immunosuppressive activity with recombinant lipocortin I produced by Escherichia coli. The culture supernatants of splenic macrophages from tumor-bearing mice suppressed the mitogenic responses in splenic lymphocytes. The culture supernatants contained higher levels of lipocortin I, but not PGE2, which was considered as a major immunosuppressive factor. Anti-lipocortin I antiserum neutralized these inhibitory activities. Natural lipocortin I purified from the spleens of tumor-bearing mice showed a potent suppressive activity, which was &gt; or = 200 times higher than that of recombinant mouse lipocortin I at protein level. Alkaline phosphatase treatment of natural lipocortin I decreased immunosuppressive activity to the level of recombinant lipocortin I. N-glycosidase F treatment failed to decrease the immunosuppressive activities. These results suggest that the protein modification of lipocortin I, possibly phosphorylation but not glycosylation, is critical for the potent immunosuppressive activity in tumor-bearing mice.
Immortalization with herpesvirus saimiri modulates the cytokine secretion profile of established Th1 and Th2 human T cell clones.
Authors: De Carli M , Berthold S , Fickenscher H , Fleckenstein I M , D'Elios M M , Gao Q , Biagiotti R , Giudizi M G , Kalden J R , Fleckenstein B 
Published: January 2023

Abstract
T blasts of six established human CD4+ T cell clones with defined Ag specificity and cytokine secretion profile (3 Th1 and 3 Th2) were immortalized with Herpesvirus saimiri (HVS) and compared with their uninfected counterparts for their ability to proliferate, produce cytokines, and express cytolytic activity. HVS-transformed Th1 and Th2 clones neither substantially changed their original surface markers nor lose their ability to proliferate in response to their specific Ag but did acquire the ability to proliferate in response to contact signals delivered by SRBC or autologous APC alone. In addition, transformation by HVS substantially enhanced the lectin-dependent cytolytic activity of Th1 clones and enabled noncytolytic Th2 clones to exert cytolytic activity. HVS-transformed Th1 clones but not their uninfected counterparts spontaneously transcribed and secreted Th1-type cytokines (IL-2, IFN-gamma, and TNF-beta) and such a production was further enhanced by stimulation with either SRBC or PMA plus anti-CD3 mAb. HVS transformed but not uninfected Th2 clones constitutively expressed both IL-4 and IL-2 mRNA and secreted IFN-gamma. Stimulation with PMA plus anti-CD3 mAb induced uninfected Th2 clones to secrete high amounts of IL-4 and IL-5 but not Th1-type cytokines, whereas the same HVS-transformed Th2 showed minimal IL-4 and IL-5 secretion with concomitant high production of IL-2, IFN-gamma, and TNF-beta. Transformation by HVS also resulted in up-regulation of TNF-alpha and IL-3 production by both Th1 and Th2 clones. The ongoing proliferation of HVS-transformed clones was partially inhibited by either anti-IL-2 or anti-IL-3 antibodies and virtually abolished by the combined addition of the two anticytokine antibodies, suggesting that both IL-2 and IL-3 can function as autocrine growth factors for HVS-transformed Th1 and Th2 clones.