bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control by Ig genes of the responsiveness to a neutralization viral B cell epitope.
Authors: Leclerc C , Martineau P , Charlot B , Delpeyroux F , van der Werf S , Hofnung M 
Published: December 2022

Abstract
In the present study, we analyzed the capacity of seven strains of mice to produce Abs against the neutralization poliovirus C3 B cell epitope, chemically or genetically linked to two different carrier proteins (MalE and keyhole limpet hemocyanin) or to recombinant hepatitis B surface Ag particles. Following immunization with these different immunogens, all strains of mice developed high Ab titers against the carrier proteins. However, only four strains of mice developed a significant Ab response against the poliovirus C3 B cell epitope. Indeed, in contrast to BALB/c, DBA/1, DBA/2, and 129 sv mice, C57BL/6, C3H, and CBA/J mice failed to produce anti-C3 Abs after immunization with the various C3 immunogens. Using various H-2 congenic strains on BALB/c or C57BL/10 background, this study clearly showed that the response to the C3 B cell epitope is not controlled by MHC genes. In contrast, analysis of anti-C3 Ab responses in IgH congenic mouse lines on BALB/c or C57BL/6 background demonstrated that the capacity to respond to this B cell epitope is controlled by genes closely linked to V(H) genes. This study therefore represents the first demonstration that the V(H) polymorphism can limit the Ab response to a viral neutralization epitope, and therefore has important implications for vaccine development.
Early production of IL-4 in susceptible mice infected with Leishmania major rapidly induces IL-12 unresponsiveness.
Authors: Launois P , Swihart K G , Milon G , Louis J A 
Published: December 2022

Abstract
Previous results have documented a burst of IL-4 mRNA that peaks in draining lymph nodes of susceptible BALB/c mice 16 h after infection with Leishmania major. The importance of this early IL-4 response in subsequent Th2 cell maturation is supported by observations showing that 1) neutralization of IL-4 at the initiation of infection or 2) administration of IL-12, which results in an inhibition of the 16 h IL-4 mRNA burst, inhibits Th2 cell development. However, both treatments are effective in hampering Th2 cell development only if given at a time when IL-4 has been produced for &lt;48 h. At this time after infection, lymph node CD4+ T cells from BALB/c mice no longer respond to IL-12. This IL-12 unresponsiveness is prevented in mice treated with anti-IL-4 Abs at the initiation of infection. Finally, the inhibition of Th2 development in BALB/c mice treated with anti-IL-4 Abs at the onset of infection results from maintenance of IL-12 responsiveness, since it requires IL-12. Together, these results reveal a narrow window of time, between 16 h and &lt;48 h after infection, during which IL-4 produced rapidly in BALB/c mice renders T cells unresponsive to IL-12, allowing their differentiation toward the Th2 phenotype.
Detection and biochemical characteristics of the receptor for complexes of soluble CD14 and bacterial lipopolysaccharide.
Authors: Vita N , Lefort S , Sozzani P , Reeb R , Richards S , Borysiewicz L K , Ferrara P , Labéta M O 
Published: December 2022

Abstract
Soluble CD14 (sCD14) has been found to bind LPS and mediate LPS activation of several cell types. It has been postulated that sCD14-LPS complexes induce cell responses by interacting with a cell surface structure, which, in turn, triggers cell activation. There has been no biochemical evidence, however, for a direct interaction of sCD14 with a cell surface structure, and the putative receptor has not been identified. To rigorously test this hypothesis, we studied the interaction of human rsCD14 with cells in the absence of serum and in the presence and the absence of LPS. We found 1) there was specific and saturable binding of 125I-sCD14, indicative of a typical receptor-ligand interaction, to several cell types, including endothelial cells, epithelial cells, astrocytes, and human monocytes; 2) specific binding to all the cell types and IL-6 induction in membrane-bound CD14 (mCD14)-negative cells occurred only when both sCD14 and LPS were present; 3) competitive displacement experiments of 125I-sCD14 binding to astrocytes and Scatchard plots revealed a binding of high affinity (Kd = 3.3 +/- 0.4 nM) and approximately 25,000 single class binding sites/cell; 4) the steady state for the association of 125I-sCD14 was obtained after 180-200 min; 5) chemical cross-linking experiments revealed the association of sCD14 with a binding structure of approximately 216 kDa; 6) binding of 125I-sCD14 to CD14-expressing cell transfectants was about 50% lower than that to nontransfected cells. Maximal binding, however, was recovered after removing mCD14, suggesting that the sCD14-LPS receptor may also interact with mCD14. These results provide direct biochemical evidence for the existence of a cell surface signal-mediating binding structure for LPS-bearing sCD14 and suggest that this structure may represent the signaling unit of the postulated multimeric LPS receptor in mCD14-bearing cells.
Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients.
Authors: Aranda R , Sydora B C , McAllister P L , Binder S W , Yang H Y , Targan S R , Kronenberg M 
Published: December 2022

Abstract
Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis.
Authors: Persidsky Y , Stins M , Way D , Witte M H , Weinand M , Kim K S , Bock P , Gendelman H E , Fiala M 
Published: December 2022

Abstract
HIV-1 invades the central nervous system early during viral infection, but neurologic impairment usually occurs years later. The strongest predictor for clinical dementia is the absolute numbers of immunocompetent brain macrophages. Thus, how monocytes penetrate the brain during disease remains critical for understanding the neuropathogenic mechanisms of HIV-1 encephalitis. To these ends, we constructed an artificial blood-brain barrier (BBB) consisting of a matrix-coated membrane with brain microvascular endothelial cells (BMVEC) on one side and astrocytes on the other. Astrocyte endfeet contacted the monolayer of BMVEC that formed tight junctions. To determine the role of viral and immune factors in monocyte penetration across the BBB, HIV-infected or uninfected monocytes with or without immune stimulation were placed onto the upper chamber of the BBB model system. Placement of immune-stimulated (LPS-treated) cells onto the BBB construct elicited gaps between BMVEC, with bulging of nuclear zones and increased numbers of vesicular Golgi complexes and endoplasmic reticulum. This correlated with a profound increase (up to 20-fold) in the number of migrating cells. Viral infection did not enhance monocyte migration. The activated monocytes showed increased numbers of philopodia, lysosomes, and vesicular Golgi complexes and expressed large levels of proinflammatory cytokines (TNF-alpha, IL-6, and IL-10). These data suggest that a major mechanism for the transendothelial migration of monocytes during HIV encephalitis is the immune activation that accompanies viral infection of the central nervous system.
Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics.
Authors: Ying S , Humbert M , Barkans J , Corrigan C J , Pfister R , Menz G , Larché M , Robinson D S , Durham S R , Kay A B 
Published: December 2022

Abstract
We recently demonstrated bronchial mucosal expression of IL-4 and IL-5 at the mRNA and protein level in both atopic and nonatopic (intrinsic) asthma. In this report, using double immunohistochemistry (IHC) and in situ hybridization (ISH), we show that 70% of IL-4 and IL-5 mRNA+ signals co-localized to CD3+ T cells, the majority (&gt;70%) of which were CD4+, although CD8+ cells also expressed IL-4 and IL-5 mRNA. The remaining IL-4 and IL-5 mRNA signals co-localized to mast cells and eosinophils. The cellular distribution of these mRNA species did not differ between atopic and nonatopic asthmatics. In contrast, double IHC showed that IL-4 and IL-5 immunoreactivity was predominantly associated with eosinophils and mast cells, with few IL-5 or IL-4 immunoreactive CD3+ T cells detectable. However, total IL-4- or IL-5-positive cells detected by IHC were &lt;40% of the total mRNA+ cells, raising the possibility that insufficient cytokine protein accumulated within T cells to enable detection by IHC. We conclude that: 1) in atopic and nonatopic asthma CD8+ T cells, in addition to CD4+ T cells, mast cells and eosinophils express mRNA for IL-4 and IL-5; 2) whereas IL-4 and IL-5 mRNA expression was associated mainly with T cells, immunoreactivity for the corresponding protein products was detectable predominantly in eosinophils and mast cells; and 3) this discrepancy may be partly attributable to the relative insensitivity of double IHC technique that does not allow detection of cytokine protein in T cells where, unlike eosinophils and mast cells, there is no facility for storage and concentration in granules.
Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage.
Authors: Blom B , Res P , Noteboom E , Weijer K , Spits H 
Published: December 2022

Abstract
Progenitor cells that seed the fetal thymus are derived from the fetal liver and the bone marrow. These cells migrate through the fetal blood to the thymus. In this work, we address which peripheral progenitor cells have the potential to become T cells and whether these progenitor cells are already committed to the T cell lineage. All CD34+CD38- precursor cells, regardless of their origin, are able to develop into T cells in a hybrid human/mouse fetal thymic organ culture. Previously, we found that the more differentiated CD34+CD38+ progenitor cells from fetal liver cannot develop into T cells. In this work, we show that CD34+CD38+ cells from fetal bone marrow and cord blood are capable of T cell development. In spite of the T cell-developing potential, we did not detect rearrangements of TCR-delta or TCR-beta loci in any of the CD34+ peripheral precursors. CD34+ fetal bone marrow cell subpopulations express pre-TCR-alpha. However, we could not detect expression of pT alpha or of recombination-activating gene 1 in CD34+ cord blood cells. Since cord blood CD34+ cells should contain the direct progenitors of the CD34+ thymocytes, our data do not support the notion that in humans commitment to the T cell lineage occurs before the cells migrate into the thymus.
Contribution of CpG motifs to the immunogenicity of DNA vaccines.
Authors: Klinman D M , Yamshchikov G , Ishigatsubo Y 
Published: December 2022

Abstract
We previously showed that bacterial DNA contains immunostimulatory motifs consisting of unmethylated CpG dinucleotides flanked by two 5' purines and two 3' pyrimidines. These motifs rapidly trigger an innate immune response, characterized by the production of IL-6, IL-12, and IFN-gamma. Since DNA vaccines are constructed from plasmids of bacterial DNA, we examined whether CpG motifs present in these plasmids contributed to the immunogenicity of DNA vaccines. In vitro experiments showed that DNA plasmids induced production of the same cytokines stimulated by bacterial DNA, an effect eliminated by DNase treatment. In vivo experiments showed that the immunogenicity of a DNA vaccine was significantly reduced by methylating its CpG motifs and was significantly increased by coadministering exogenous CpG-containing DNA. These findings support the conclusion that CpG motifs in the plasmid backbone of DNA vaccines play an important role in the induction of Ag-specific immunity.
MHC class II molecules are required for initiation of positive selection but not during terminal differentiation of human CD4 single positive thymocytes.
Authors: Vanhecke D , Verhasselt B , De Smedt M , De Paepe B , Leclercq G , Plum J , Vandekerckhove B 
Published: December 2022

Abstract
Positive selection of T cell precursors is an MHC dependent, multistep process by which functionally mature CD4+8- helper and CD4-8+ cytotoxic single positive (SP) T cells are generated from immature CD4+8+ double positive (DP) thymocytes. We investigated the requirement for TCR/MHC class II interactions during different stages of positive selection of human CD4 SP thymocytes. We show that sorted CD69- CD4+8+ DP preselection thymocytes cultured in fetal thymus lobes of normal mice were subject to positive selection and differentiated to CD3(high) CD69+, mature CD8 SP, and CD4 SP cells. When cultured in thymus lobes from MHC class II-deficient mice, these precursors failed to develop into mature CD4 SP T cells, indicating that in the hybrid cultures, murine MHC class II molecules are required for the development of mature human CD4 SP T cells. We have previously identified CD4 SP intermediate thymocytes that have received at least some of the signals involved in positive selection, since these cells are CD69+, CD3/TCR(high), and CD8beta- but that are still phenotypically and functionally immature. Here we demonstrate that in contrast to preselection thymocytes, these CD4 SP intermediate thymocytes can give rise to phenotypically mature and functionally CD4 SP progeny both in normal and in MHC class II-deficient thymus lobes. These results suggest that TCR/MHC interactions are required for the initial stages of positive selection, but are not essential during terminal differentiation to functionally mature CD4 SP T cells.
Functional responses and apoptosis of CD25 (IL-2R alpha)-deficient T cells expressing a transgenic antigen receptor.
Authors: Van Parijs L , Biuckians A , Ibragimov A , Alt F W , Willerford D M , Abbas A K 
Published: December 2022

Abstract
IL-2 was initially defined as a T lymphocyte growth factor, but recent studies have provided evidence that it may also play a role in regulating T cell differentiation, apoptosis, and tolerance. To examine the contribution of IL-2 to these processes, we have bred a class II-restricted TCR transgene into mice deficient in the alpha-chain of the IL-2R, CD25. We show that in response to Ag, T cells from these mice are unable to use IL-2 and, as a result, are less efficient at traversing the cell cycle, and proliferate less than wild-type cells. Furthermore, CD25 -/- T cells exhibit reduced survival in vitro, even in the presence of costimulatory signals. IL-4 and IL-15, a cytokine related to IL-2, enhance the survival and Ag-induced proliferation of CD25 -/- T cells. Activated CD25 -/- T cells are resistant to Fas-mediated activation-induced cell death (AICD), and this defect cannot be corrected by other cytokines. Therefore, IL-2 plays a unique role in regulating AICD, but has redundant roles in T cell survival and proliferation in vitro. The failure of AICD observed with CD25 -/- T cells may explain the unexpected observation that deficiency of IL-2 or of the alpha- or beta-chain of the IL-2R results not in immunodeficiency, but in autoimmune disease.
Distinct phenotype of leukemic T cells with various tissue tropisms.
Authors: Tanaka Y , Wake A , Horgan K J , Murakami S , Aso M , Saito K , Oda S , Morimoto I , Uno H , Kikuchi H , Izumi Y , Eto S 
Published: December 2022

Abstract
There is an emerging concept, the validity of which remains to be proven, that preferential expression of selective adhesion molecules on particular T cell subsets may result in tissue-specific migration. L-selectin, cutaneous lymphocyte-associated Ag (CLA), and integrin alpha4beta7 are proposed to be involved in selective migration of T cell subsets into peripheral lymph nodes, skin, and gastrointestinal mucosa, respectively. Adult T cell leukemia (ATL) is associated with lymphoid infiltration of tissues and secondary lymphoid organs. To clarify the role of these putative homing molecules in vivo, we assessed their expression on circulating ATL cells from patients with lymph node, skin, and gut involvement. L-selectin expression was significantly higher on peripheral ATL cells in patients with lymphadenopathy than in patients without it. CLA was highly expressed on peripheral ATL cells compared with normal T cells: its expression was also significantly higher on peripheral ATL cells from patients with skin involvement compared with cells from patients without it. beta7 was particularly highly expressed on peripheral ATL cells from patients with gastrointestinal involvement. In summary, the differential expression of beta7 and beta1 on peripheral ATL cells correlates with the presence of gastrointestinal involvement. Similarly, the presence of skin involvement is associated with the expression of CLA(high)beta7low on peripheral ATL cells. These results, which are consistent with the molecules CLA and alpha4beta7 mediating preferential T cell migration to the skin and gastrointestinal mucosa, respectively, may allow for a refinement of the classification of lymphoid neoplasms on the basis of differential expression of homing molecules.
Serum amyloid P component forms a stable complex with human C5b6.
Authors: Barbashov S F , Wang C , Nicholson-Weller A 
Published: December 2022

Abstract
A 30,000 m.w. protein bound tightly to C5b6, which was formed by activating C7-depleted human serum with zymosan. The protein remained bound to the C5b6 complex during the isolation procedure for C5b6, including chromatography on lysine-Sepharose and an anion exchange resin. Following electrophoresis and electroblotting of the C5b6 complex to a polyvinylidene difluoride transfer membrane, the 30,000 m.w. protein was microsequenced. The 24 N-terminal amino acid sequence was determined and showed identity of the 30,000 m.w. protein with the serum amyloid P (SAP) component. The C5b6-SAP complex did not dissociate in the presence of 10 mM EDTA, which distinguishes SAP-C5b6 binding from SAP's usual Ca2+-dependent binding to other molecules. SAP, which was isolated from serum by chromatography, was able to bind to preformed C5b6, which had been assembled and isolated from purified components. Functionally, the C5b6-SAP could bind C7, and the resulting C5b67-SAP complex had only moderately lower specific hemolytic activity than that of C5b67. In addition, hemolytically inactive C5b67-SAP, such as hemolytically inactive C5b67, was chemotactically active for neutrophils, while isolated SAP had no effect on cell mobility. Because SAP reacts with other serum proteins and with cells, it is likely that the addition of SAP to terminal complement complexes may affect the fate of these complexes.
Lipopolysaccharide induces synthesis of mouse colony-stimulating factor-1 in vivo.
Authors: Roth P , Bartocci A , Stanley E R 
Published: December 2022

Abstract
CSF-1 is a hemopoietic growth factor that regulates the survival, proliferation, and differentiation of mononuclear phagocytes, cells that are critical in the inflammatory response. In the case of Gram-negative infection, LPS plays an important role by inducing several cell types to produce the proinflammatory cytokines, IL-1, IL-6, and TNF-alpha. In this study, we examined the effects of i.p. administration of LPS on CSF-1 expression in the mouse. Two- to sevenfold increases in the CSF-1 concentrations determined by RIA were evident within hours of LPS administration in serum, liver, kidney, lung, spleen, brain, intestine, and heart. While alterations in the CSF-1 receptor-mediated clearance of CSF-1 appeared not to account for the increased growth factor concentrations in LPS-treated animals, there was an early LPS-induced reduction of splenic [125I]CSF-1 uptake consistent with tissue-specific down-modulation of CSF-1 receptors. The results of Northern analysis revealed increased expression of a CSF-1 mRNA species in liver, lung, kidney, spleen, intestine, and heart following LPS treatment, demonstrating that increased synthesis was responsible for the increased tissue CSF-1 concentrations. The increased expression and synthesis of CSF-1 in response to LPS may be essential for mobilizing and activating mononuclear phagocytes in the inflammatory response.
A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes.
Authors: Winter C C , Long E O 
Published: December 2022

Abstract
To examine the structural basis for the specific recognition of the MHC class I allotypes HLA-Cw*0401 and HLA-Cw*0304 by the killer cell inhibitory receptors (KIR) cl42 and cl43, respectively, mutant KIR-Ig fusion proteins were tested by direct binding to cells transfected with single HLA-C alleles. The putative loop region at position 44-46 of KIR contained amino acids that were necessary for the discrimination between HLA-Cw*0401 and HLA-Cw*0304. Surprisingly, exchanging the methionine at position 44 in cl42 with the lysine at position 44 in cl43 was sufficient to switch the specificity of cl42 from HLA-Cw*0401 to HLA-Cw*0304, and vice versa. Thus, a single amino acid in the first Ig domain of these KIR determines their ability to discriminate between the two groups of HLA-C allotypes.