bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular localization of CD4 in the human placenta. Implications for maternal-to-fetal transmission of HIV.
Authors: Lairmore M D , Cuthbert P S , Utley L L , Morgan C J , Dezzutti C S , Anderson C L , Sedmak D D 
Published: December 2022

Abstract
CD4 is a 55-kDa glycoprotein that serves as an important cellular differentiation Ag and cell signaling protein on T lymphocytes, as well as a principal receptor for HIV-1 on a variety of cell types including lymphocytes. CD4 receptor expression in syncytiotrophoblasts, the principal cellular barrier in the human placenta, has not been clearly defined. Knowledge concerning the expression of the CD4 receptor on placental trophoblasts is important to define potential mechanisms of transmission of the virus between maternal blood and fetal tissues. Both mature and immature placenta (n = 10) were examined using an avidin D-based immunohistochemical procedure that permits clear morphologic distinction of cell types in placental sections. Syncytiotrophoblasts were defined using anti-cytokeratin mAb (AE1/3), whereas endothelial cells in placental villi were distinctly identified using a mAb directed to CD31. Placental Hofbauer cells (macrophages) and other leukocytes were identified by mAb staining of leukocyte common Ag (CD45). CD4 expression (identified by staining with three separate anti-CD4 mAb) was exclusively localized using this immunohistochemical method to leukocytes in placental villi (e.g., Hofbauer cells); however, no CD4 staining was evident in syncytiotrophoblasts, cytotrophoblasts, or villus endothelial cells. Furthermore, immunoaffinity-purified trophoblasts were negative for CD4 receptor expression. CD4 RNA was not identified in purified trophoblasts using both Northern blot assay and a sensitive polymerase chain reaction method to identify CD4 RNA. In addition, time course studies of purified trophoblasts immediately after purification and at 24, 48, and 72 h in culture indicated that CD4 RNA was not present as a transient, but labile transcript in trophoblasts. These data indicate that the transmission of HIV-1 across syncytiotrophoblasts may occur by mechanisms other than by binding the CD4 receptor and that tissue leukocytes (in particular Hofbauer cells) are likely the principal CD4+ cellular target of HIV-1 in the placenta.
Presentation of beta-cell antigens to CD4+ and CD8+ T cells of non-obese diabetic mice.
Authors: Shimizu J , Kanagawa O , Unanue E R 
Published: December 2022

Abstract
We isolated CD4+ and CD8+ T cell clones from pancreatic islets of non-obese diabetic (NOD) mice and studied their interactions with pancreatic islets, in culture. The three CD4+ T cell clones proliferated when cultured with islet cells from NOD, BALB/c, or C57BL/6 (B6) mice. For proliferation to the allogeneic islets, however, APC from NOD mice were required in the culture. Two of the clones also produced IFN-gamma upon culture with NOD islet cells. The Ag from islet cells responsible for T cell stimulation were not released into the supernatant but were cell associated. Paraformaldehyde treatment of islet cells, in fact, preserved their antigenicity. The fixed islet cells could present Ag to CD4+ T cell clones, provided live, syngeneic APC were added to the culture. We conclude from these experiments that islet cells donate Ag to the APC for presentation and that the function of APC is to process the Ag. The two CD8+ T cell clones proliferated and released IFN-gamma upon reaction with islet cells from either NOD or BALB/c but not B6 mice. The CD8+ T cell clones also reacted with the insulinoma NIT-1 cell line, derived from NOD mice. Fixation of NIT-1 cells did not impair recognition when live APC were present in the culture. In this case, however, the APC could be allogeneic. We conclude that CD8+ T cells directly recognized a MHC class I-restricted Ag on target cells, but needed the costimulatory effect of APC. We also found that CD8+ T cells killed islet cells. Two of the CD4+ T cell clones produced diabetes when transferred into male, irradiated NOD mice. For optimal transfer of disease, the CD4+ T cell clones had to be co-injected with CD8+ T cells from NOD diabetic mice. The two CD8+ T cell clones did not transfer disease.
Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells.
Authors: Curiel T J , Krug E C , Purner M B , Poignard P , Berens R L 
Published: December 2022

Abstract
Infection with Toxoplasma gondii is an important cause of morbidity and mortality throughout the world. In immunocompetent hosts, the infection is usually not significant. However, infection occurring in neonates or other individuals with defective cellular immunity (such as recipients of organ allografts or persons with AIDS) may be life threatening. An effective vaccine to prevent toxoplasmosis, or immunotherapy for persons already infected with Tg would be important additions to the therapeutic armamentarium. We cloned toxoplasma-specific CTL from the PBMC of an asymptomatic individual with serologic evidence for prior Tg infection by stimulation with Ag produced from the RH strain of Tg. These CTL were exclusively of the CD3+, CD4+, CD8- surface phenotype, and lysed autologous target cells that had been either pulsed with Toxoplasma Ag, or infected with live tachyzoites. Lysis of target cells was inhibited by incubation of CTL with anti-T cell antibody, or by incubation of target cells with anti-DR antibody or chloroquine. These CTL also lysed target cells either pulsed with Ag derived from C strain Tg or infected with live C strain tachyzoites, indicating cross-reactivity of recognition. Unlike recently reported murine or human CD8+ Tg-specific CTL, which lysed tachyzoites in an extracellular, and hence HLA-unrestricted environment, these CD4+ CTL had no effect on the infectivity of extracellular tachyzoites. CD8+ Tg-specific CTL were not derived from this donor despite several different approaches to their generation. These data confirm previous reports of human Tg-specific CTL, and extend these observations to include CD4+ CTL. These findings suggest that specific immunotherapy directed against Tg, as well as the development of a preventive vaccine, may be possible.
Peritoneal gamma delta T cells induced by Escherichia coli infection in mice. Correlation between Thy-1 phenotype and host minor lymphocyte-stimulating phenotype.
Authors: Takada H , Hiromatsu K , Matsuzaki G , Muramori K , Nomoto K 
Published: December 2022

Abstract
We found that gamma delta T cells increased in number in the peritoneal cavity after i.p. inoculation with Escherichia coli (ATCC 26) in mice. The increase of the gamma delta T cells was most prominent on day 5 after inoculation when the pathogens had been already eliminated from the hosts. Two-color flow cytometric (FCM) analysis revealed that these gamma delta T cells in infected C57BL/6 mice expressed Thy-1 Ag on their cell surface. On the other hand, gamma delta T cells induced by E. coli inoculation in C3H/He mice contained Thy-1-negative gamma delta T cells in addition to the Thy-1-positive gamma delta T cells. In both strains, irrespective of Thy-1 Ag expression, these gamma delta T cells were CD5 negative, CD44 positive, L-selectin negative, Ly-6C negative, and IL-2R low positive. Analyses of peritoneal exudate cells (PEC) from several other strains of mice after E. coli inoculation suggested that Thy-1-negative gamma delta T cells appear in mice carrying endogenous superantigen specific for V beta 3, especially mammary tumor virus-6. These findings suggest that Thy-1 Ag expression on the gamma delta T cells appearing in the peritoneal cavity after i.p. E. coli inoculation is correlated to the Mls phenotype of the host mice.
Synergism between IFN-gamma and IL-1 alpha/beta in growth inhibition of an allografted tumor.
Authors: Takikawa O , Oku T , Yasui H , Yoshida R 
Published: December 2022

Abstract
Soluble effector molecules involved in the rejection of allografted mouse Meth A (3-methylcholanthrene-induced ascites type tumor) cells were examined. A potent antiproliferative activity against the tumor cells was detected in the culture supernatant of leukocytes that had infiltrated into the peritoneal cavity of C57BL/6 mice on days 6-8 after transplantation, when the i.p. transplanted Meth A cells were undergoing rejection. Studies with neutralizing antibodies indicated that both IFN-gamma and IL-1 alpha/beta were required for the activity but that TNF-alpha was not. Actually, mouse rIFN-gamma and rIL-1 alpha/beta used, at the concentrations found in the culture supernatant determined by ELISA, were able to reconstitute the potent antiproliferative activity, although each cytokine alone had a weak growth inhibitory activity against Meth A cells. The half-maximal inhibition was observed with 0.02-0.03 U/ml of rIL-1 alpha/beta at 1-100 U/ml of rIFN-gamma. The synergistic growth inhibitory effect of these cytokines also was observed with four of 15 mouse transformed cell lines tested, indicating that the effect was not specific to Meth A cells. These findings suggest that IFN-gamma and IL-1 alpha/beta participate as soluble effector molecules in the rejection of some allografted tumor cells including Meth A cells.
Leukotriene B4 mediates substance P-induced granulocyte infiltration into mouse skin. Comparison with antigen-induced granulocyte infiltration.
Authors: Iwamoto I , Tomoe S , Tomioka H , Yoshida S 
Published: December 2022

Abstract
Substance P, a potent proinflammatory peptide present in sensory neurons, causes granulocyte (neutrophil and eosinophil) infiltration into mouse skin by inducing mast cell degranulation. However, the mediator responsible for this granulocyte infiltration has not been determined. In this study, we determined which mediator from cutaneous mast cells mediates substance P-induced granulocyte infiltration in the skin by the use of two mediator antagonists; one for platelet activating factor (PAF) CV-6209 and the other for leukotriene B4 (LTB4) ONO-4057. Subcutaneous injection of substance P (10(-7)-10(-5) M) caused granulocyte infiltration in the skin of BALB/c mice in a time- and concentration-dependent fashion. Pretreatment with the LTB4 antagonist decreased substance P-induced neutrophil and eosinophil infiltration into mouse skin at 6 h to the same extent that an inhibitor of mast cell degranulation, disodium cromoglycate, decreased those responses. However, pretreatment with the PAF antagonist affected neither substance P-induced neutrophil nor eosinophil infiltration at 6 h. A LTC4/D4 antagonist ONO-1078 and a histamine H1 antagonist chlorpheniramine had no effect on the granulocyte infiltration, either. The LTB4 antagonist also decreased substance P-induced neutrophil, but not eosinophil, infiltration into mouse skin at 24 h. In contrast, the PAF antagonist inhibited Ag-induced eosinophil infiltration of mouse skin, whereas the LTB4 antagonist inhibited the Ag-induced neutrophil infiltration. We conclude that LTB4 is a major mast cell-derived chemotactic mediator for initiating substance P-induced neutrophil and eosinophil infiltration into mouse skin. Our results suggest that LTB4 antagonists might be useful in preventing such neurogenic inflammation.
Biotinylation of monoclonal antibodies prevents their ability to activate the classical pathway of complement.
Authors: Jokiranta T S , Meri S 
Published: December 2022

Abstract
Biotinylation of mAb has become a standard procedure for a variety of applications that exploit the specific high affinity interaction between biotin and avidin. In the present study, we investigated how biotinylation of mAb affects their ability to sensitize target cells to C-dependent lysis in vitro. mAb were biotinylated by cross-linking biotin covalently with an N-succinimidyl ester to the epsilon-amino groups of lysine residues. Human RBC were treated with two rat mAb, either alone or together: one against glycophorin A (YTH89.1), another against CD59 (protectin; YTH53.1), an inhibitor of the membrane attack complex of C. Melanoma cells (G361) were attacked by a mouse mAb (27A) against an O-acetylated GD3 ganglioside. As compared with the nonbiotinylated mAb, the biotinylated forms of all the investigated mAb were much weaker in causing classical C pathway-mediated lysis of the target cells. Biotinylation did not reduce the ability of the mAb to bind to their Ag, nor of the anti-CD59 mAb to neutralize the C lysis-restrictive effect of CD59. In binding assays using 125I-labeled C1q, significantly less C1q bound to the biotinylated anti-glycophorin-A and anti-CD59 mAb than to the nonbiotinylated mAb. These data show that biotinylated antibodies do not activate the classical C pathway because binding of C1q to the antibody Fc-regions is blocked.
Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4.
Authors: Wertheim W A , Kunkel S L , Standiford T J , Burdick M D , Becker F S , Wilke C A , Gilbert A R , Strieter R M 
Published: December 2022

Abstract
Historically, the neutrophil has been perceived as a terminally differentiated leukocyte with limited ability to produce de novo proteins. Furthermore, in the context of acute inflammation the activated neutrophil has been appreciated only for its ability to release various proteases, reactive oxygen, and arachidonic acid metabolites. Recently, the neutrophil has been shown to have the capacity to produce a number of cytokines that may be instrumental in orchestrating the progression of acute inflammation to a more chronic and specific immune response. These cytokines include IFN-alpha, M-CSF, G-CSF, TNF, IL-1, and IL-6. Our laboratory and others have shown that neutrophils produce IL-8 in response to LPS or a phagocytic challenge. Although these studies have shown the induction of IL-8 from polymorphonuclear neutrophils (PMN), relatively little is known regarding the regulation of PMN-derived IL-8. Because PMN and monocytes share the same stem cell, and monocyte-derived IL-8 is regulated by prostaglandin E2 (PGE2), glucocorticoids (dexamethasone; DEX) and the T-Lymphocyte-derived IL-4, we postulated that PMN-derived IL-8 production may be regulated in a similar manner. To test this hypothesis, PMN were isolated (&gt; 99% pure) from peripheral blood and cultured in media with 5% FCS in the presence or absence of LPS (10 ng/ml; a concentration of LPS that induced the half-maximal production of PMN-derived IL-8) and in the presence or absence of DEX (10(-6) M to 10(-10) M), PGE2 (10(-6) M to 10(-10) M), or IL-4 (100 ng/ml to 100 pg/ml). PMN-derived IL-8 was measured using a specific sandwich ELISA. DEX and IL-4 in the presence of LPS were found to inhibit PMN-derived IL-8 in both a dose- and time-dependent fashion. DEX and IL-4 in concentrations of 10(-6) M and 10 ng/ml resulted in maximal inhibition of LPS-induced PMN-derived IL-8, respectively. Moreover, both DEX and IL-4 administration could be delayed 4 hr post-stimulation with LPS and result in significant suppression of PMN-derived IL-8. Interestingly, in contrast to the regulation of monocyte-derived IL-8 by PGE2, PGE2 treatment of PMN failed to inhibit the generation of LPS-induced IL-8. Northern blot analysis of steady-state IL-8 mRNA demonstrated that both DEX and IL-4 treatment of PMN resulted in a 40 and 52% reduction in LPS-stimulated PMN-derived IL-8 mRNA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
HIV-induced loss of CD44 expression in monocytic cell lines.
Authors: Guo M M , Hildreth J E 
Published: December 2022

Abstract
We have found that HIV-1 infection of monocytic cell lines results in a new adhesion phenotype. Whereas uninfected cells grow as single cell suspensions, HIV-infected cells grow as large aggregates. When the expression of adhesion molecules was investigated, CD44 was almost completely depleted from the surface of HIV-infected cells. Immunoprecipitation with mAb confirmed the loss of CD44 from the surface of infected cells. In addition, loss of surface CD44 was not due to formation of internal complexes or release into the culture supernatant. Soluble CD44 was not detected in culture supernatant from HIV-infected cells. Northern blot analysis showed an altered RNA pattern in HIV-infected cells. The high molecular mass CD44 RNA (7.0 kb) was lost from infected cells, and the low molecular mass CD44 RNA (1.2 kb) remained. We have previously shown that anti-CD44 mAb induces homotypic adhesion in CD44+ cell lines. In this report, we show that homotypic adhesion of the HIV-infected cells occurs through a different mechanism than anti-CD44 mAb-induced aggregation. The homotypic adhesion in infected cells was CD18-mediated, but anti-CD44 mAb-induced homotypic adhesion in uninfected cells was CD18-independent. The change in adhesion phenotype and the loss of CD44 from the surface of HIV-1-infected monocytic cells are discussed in terms of their potential implications in cell-to-cell transmission of HIV.
Concurrent infection of human macrophages with HIV-1 and Mycobacterium avium results in decreased cell viability, increased M. avium multiplication and altered cytokine production.
Authors: Newman G W , Kelley T G , Gan H , Kandil O , Newman M J , Pinkston P , Rose R M , Remold H G 
Published: December 2022

Abstract
The effects of a concurrent HIV-1 and Mycobacterium avium infection in vitro were assessed in human peripheral blood-derived macrophages (M phi). M phi were infected with HIV-1Ba-L strain for 14 days then infected with M. avium (HIV/M. avium) or treated with LPS (HIV/LPS). At various times after M. avium or LPS treatment, Mo phi cultures were harvested for quantitation of HIV and M. avium replication, as well as M phi cellular viability. In addition, mRNA and supernatants were collected for assessment of induction of the cytokines TNF-alpha, IL-1 beta and IL-6. M. avium multiplication was greater in HIV-infected M phi, whereas no difference in virus production, based on p24 and RT values, was observed between HIV-infected cells and HIV/M. avium or HIV/LPS M phi. M. avium infection of HIV-1-infected M phi also caused a decrease in viability of the M phi. HIV-1/M. avium-infected M phi had a 24 h delay in induction of TNF-alpha steady state mRNA when compared with HIV/LPS or M. avium only or LPS-only treated M phi. HIV infection also increased the amount and the length of induction of IL-1 beta and IL-6 steady state mRNA stimulated by either M. avium or LPS. In addition, prolonged and increased protein production of TNF-alpha, IL-6, and IL-1 beta was observed in HIV/M. avium-infected cells when compared with the other treatments. In direct contrast to M. avium infection, no significant differences in LPS-induced protein production of the three cytokines was observed between HIV-1-infected and -noninfected M phi. Treatment of HIV/M. avium-infected cells with human rGM-CSF did not increase either the time or quantity of induction of TNF-alpha mRNA or protein production in HIV/M. avium-infected M phi. The increase in M. avium numbers, dysregulation of cytokine production, and subsequent cell death seen in vitro in HIV/M. avium-infected human M phi may reflect part of the underlying cause of the highly disseminated M. avium disease pattern observed in AIDS patients.
Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product.
Authors: Asano Y , Brach M A , Ahlers A , de Vos S , Butterfield J H , Ashman L K , Valent P , Gruss H J , Herrmann F 
Published: December 2022

Abstract
Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently identified stem cell factor, was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10(-9) M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN-gamma, vitamin D3, retinoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.
Reduced CD3-mediated protein tyrosine phosphorylation in anergic CD4+ and CD8+ T cells.
Authors: Bhandoola A , Cho E A , Yui K , Saragovi H U , Greene M I , Quill H 
Published: December 2022

Abstract
Mice inoculated i.v. with superantigens exhibit long lived Ag-specific T cell tolerance. An in vitro model for this phenomenon is the ensuing unresponsiveness of Th1 T cell clones activated via the TCR/CD3 complex in the absence of co-stimulation. We have previously demonstrated alterations in TCR-mediated early protein tyrosine phosphorylation events in Th1 clones anergic for IL-2 production. In this study, we demonstrate unresponsiveness in CD4+ and CD8+ T cells from V beta 8.1 transgenic mice inoculated i.v. with the superantigen Mls-1a. The unresponsiveness of both CD4+ and CD8+ T cells involves defective IL-2 production upon restimulation, with CD4+ T cells exhibiting an additional defect in IL-2 utilization. The transgenic model allowed study of T cell signaling in a relatively homogeneous population of unresponsive cells without elaborate purification of Ag-reactive populations. Both CD4+ and CD8+ T cells exhibit altered tyrosine phosphorylation of two protein substrates upon CD3-mediated restimulation. The substrates involved, p38 and p75, are of identical size to substrates similarly affected in anergic Th1 clones. Altered tyrosine phosphorylation is therefore closely associated with defective IL-2 production in these three anergic T cell types, and may play a role in the maintenance of anergy.
Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family.
Authors: Fleming T J , Fleming M L , Malek T R 
Published: December 2022

Abstract
Mouse Ly-6 proteins are characterized by lineage-restricted patterns of expression on lymphoid cells. A mAb (1A8) was produced to Ly-6G, a newly described member of the Ly-6 locus. Based on selective reactivity to cloned Ly-6 gene products expressed in EL4J cells, 1A8 was determined to be specific for Ly-6G. Furthermore, mAb to other Ly-6 specificities did not bind to Ly-6G-transfected EL4J cells, indicating that Ly-6G is distinct from other serologically defined Ly-6 specificities. FACS analysis using 1A8 demonstrated that Ly-6G was expressed in bone marrow but not substantially on other lymphoid tissues, including activated T and B cells. In the bone marrow, Ly-6G expression was primarily restricted to the cells with more forward angle light scatter, which are mostly granulocytes. The RB6-8C5 mAb, previously described to detect a myeloid-restricted Ag (Gr-1) on more differentiated granulocytes, also reacted with Ly-6G- and Ly-6C-transfected EL4J cells. Both 1A8 and RB6-8C5 selectively precipitate a M(r) 21 to 25 kDa, glycosylphosphatidylinositol-anchored protein. Collectively, these data indicate that the Gr-1 Ag is a member of the Ly-6 family and further link expression of individual Ly-6 genes with distinct lineages in mouse bone marrow cells.