bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of rat gamma/delta T lymphocytes in peripheral lymphoid organs, small intestine, and skin with a monoclonal antibody to a constant determinant of the gamma/delta T cell receptor.
Authors: Kühnlein P , Park J H , Herrmann T , Elbe A , Hünig T 
Published: December 2022

Abstract
A mAb called V65 was raised to a CD3+, TCR-alpha/beta- rat/mouse T cell hybrid that selectively reacts with all CD3+, TCR-alpha/beta- rat lymphocytes. Both anti-CD3 and V65 precipitate a 48- to 50-kDa heterodimeric protein from digitonin-lysed surface-iodinated cells. V65+ but not V65- T cells and T cell hybridoma cells express TCR-gamma mRNA. Together, these results show that V65 detects a constant determinant of the rat TCR-gamma/delta. In the presence of either IL-2 or IL-4, V65 stimulates proliferation in peripheral rat gamma/delta T cells. Approximately 90% of gamma/delta T cells from peripheral lymphoid organs have the same cell surface phenotype as thymus-derived MHC class I-restricted alpha/beta T cells, i.e., they are CD4- but express the CD8 alpha/beta heterodimer together with CD2 and CD5. In contrast, gamma/delta T cells from the epithelium of the small intestine lack CD2, CD4, and CD5 and express CD8 alpha only. Finally, V65 directly identifies a dense network of dendritic cells in the epidermis as gamma/delta T cells. These dendritic epidermal T cells are absent from athymic rats, indicating that like their mouse counterparts, they are thymus dependent.
Stage-specific expression of activation antigens on NK cells at uterine implantation sites in mice.
Authors: Linnemeyer P A , Pollack S B 
Published: December 2022

Abstract
The differentiation of the cellular components of the uterine decidua, in particular the life history of NK cells, is poorly understood. With the use of two mAbs that recognize stage-specific activation Ags on NK cells, we investigated the development of NK cells known as granulated metrial gland (GMG) cells. Immunohistochemical analysis demonstrated that mAb 3C2, but not mAb 4H12, recognized numerous cells throughout the uterine decidua basalis during early gestation. Isolated (panned) 3C2+ decidual cells from day 7 of pregnancy co-expressed the NK1.1 Ag, displayed NK cytolytic activity, and proliferated in IL-2-containing media. A small percentage of those cells expressed the GMG-associated Ag 4H12. Immunohistochemical analysis of serial sections at midgestation demonstrated that most of the 3C2+ NK cells co-expressed 4H12 Ag. During the later part of pregnancy, however, 3C2 expression in the decidua was down-regulated, and the cells expressed high levels of 4H12 Ag. When 3C2+ NK cells were isolated from cell suspensions of decidua from 7-day pregnant mice, and cultured in IL-2-containing medium, the cells developed the large and granular morphology characteristics of GMG cells, and acquired 4H12 Ag. These results demonstrate that 4H12+ GMG cells differentiate from 3C2+, NK1.1+, cytolytic precursors that reside in the decidua during early gestation.
Invariant chain prevents the HLA-DR-restricted presentation of a cytosolic peptide.
Authors: Long E O , LaVaute T , Pinet V , Jaraquemada D 
Published: December 2022

Abstract
Three properties of the HLA-DR-associated invariant chain (Ii) may contribute to the distinction between the class I and class II Ag presentation pathways. First, Ii prevents peptide binding to alpha beta 1 Ii complexes. Second, Ii promotes assembly of class II alpha beta heterodimers and their transport out of the endoplasmic reticulum. Third, Ii provides a targeting signal for the transport of class II molecules to endocytic compartments. However, it is not known whether Ii can prevent class II-restricted T cell recognition of endogenous peptides transported into the endoplasmic reticulum. In addition, recent evidence has indicated that, in the absence of Ii, newly synthesized class II molecules cannot form stable complexes with peptides. In this study, transfected human fibroblast cells expressing HLA-DR1 alone or with an excess of Ii were tested for their ability to present a DR1-restricted epitope of the influenza virus matrix protein produced as a short cytosolic peptide by use of an episomal expression vector. Presentation to a DR1-restricted T cell clone was very efficient in cells expressing class II molecules without Ii, but not in cells expressing class II and Ii. The inhibition by Ii was specific for the endogenous cytosolic peptide, because the same epitope processed from exogenous influenza virus particles was presented only by cells expressing class II with Ii. Ii did not inhibit the HLA-A2-restricted presentation of another cytosolic peptide. Thus, T cells can detect a cytosolic peptide loaded onto class II alpha beta heterodimers, and Ii prevents such endogenous peptide presentation.
Helper T cell-independent proliferation of CD8+ cytotoxic T lymphocytes transduced with an IL-1 receptor retrovirus.
Authors: Nagoya S , Greenberg P D , Yee C , Weisser K E , Sugawara H , Widmer M B , Slack J , Dower S K , Lupton S D , Overell R W 
Published: December 2022

Abstract
Although the proliferation of CD8+ CTL typically requires cytokine support provided by helper T cells, a subset of naturally occurring CD8+ CTL are capable of proliferating independently of T cell help. Such helper-independent CTL have previously been shown to possess IL-1 receptors (IL-1R) and to proliferate in response to IL-1 through endogenous production of IL-2. In this study, we have transduced conventional helper-dependent CTL clones with a retroviral vector encoding the murine type I IL-1R. Transduced CTL selected in G418 expressed vector-derived transcripts encoding IL-1R and displayed approximately 1000 cell surface receptors with an IL-1 affinity typical for the type I IL-1R. In contrast to parental cells, transduced CTL proliferated in response to IL-1 in the presence of Ag, without a requirement for helper T cells, IL-2, or other cytokine support. Stimulation with both IL-1 and Ag was necessary for the proliferative response. No endogenous synthesis of IL-2 could be detected in the IL-1R transduced cells in response to IL-1 stimulation, in the presence or absence of Ag. The IL-1R-induced phenotype was demonstrated in two independent T cell clones, both of which retained Ag-specific cytolytic activity. No such conversion to a helper-independent phenotype was induced by a retroviral vector encoding only the neo gene. The behavior of the IL-1R-transduced CTL in proliferation assays thus resembled that of the naturally occurring helper-independent CTL.
Developmental regulation of the TCR zeta-chain. Differential expression and tyrosine phosphorylation of the TCR zeta-chain in resting immature and mature T lymphocytes.
Authors: Rozdzial M M , Kubo R T , Turner S L , Finkel T H 
Published: December 2022

Abstract
The zeta subunit of the TCR complex targets receptor surface expression, is phosphorylated on tyrosine residues upon T cell activation, and is implicated in signal transduction after TCR ligation. Here we show that, although intrathymic expression of the murine TCR-associated zeta-chain relative to the other chains of the Ag receptor complex remains unchanged during early thymocyte development, there is a doubling of TCR-associated zeta-chain surface expression upon thymocyte maturation. The ratio of tyrosine-phosphorylated relative to nonphosphorylated TCR-associated zeta-chain also changes with thymocyte development. This ratio was quantified after the purification and detergent extraction of receptor complexes from freshly isolated immature or mature thymocytes. Immunoprecipitation of the zeta-chain released from the complex allowed for the isolation of the tyrosine-phosphorylated and nonphosphorylated forms of TCR-associated zeta-chain. Intracellular free zeta-chain was characterized by immunoprecipitation after clearing the cell lysate of intact TCR complexes. Densitometric analysis of immunoblots indicated that surface phosphorylated zeta-chain is more abundant in immature relative to mature T cell populations, whereas the inverse is true of intracellular phosphorylated zeta-chain. Surface phosphorylated zeta-chain also migrated at a higher m.w. than its cytoplasmic counterpart, suggesting that it is more highly modified on some or all of its available tyrosines. These findings demonstrate that the stoichiometry and post-translational modification of the TCR complex are regulated, in vivo, and may determine the functional maturation of T cell signaling, selection, and activation.
Cells infected with Yersinia present an epitope to class I MHC-restricted CTL.
Authors: Starnbach M N , Bevan M J 
Published: December 2022

Abstract
Bacteria of the genus Yersinia cause disease in humans ranging from enteritis and lymphadenitis to plaque. These organisms have the ability to bind to host cells and, in a complex interaction, are able to deliver a specific subset of proteins into the host cell. These proteins alter host structures and functions, and in the case of macrophages, prevent phagocytosis of the organism. In Yersinia enterocolitica, one of these proteins, Yop51, is known to be a protein tyrosine phosphatase. By using a directed approach, we have raised murine CTL that recognize a peptide epitope from Yop51 in the context of the MHC class I molecule H-2 Db. This epitope, Yop51 249-257, seems to be presented both by cells that produce Yop51 endogenously and by epithelial cells infected with virulent Y. enterocolitica. In vivo, Y. enterocolitica is believed to remain mostly in an extracellular niche. Therefore, detection of this organism by cytotoxic T cells and, possibly, resistance to disease may depend on recognition of epitopes from a subset of virulence determinants delivered into the cytoplasm of host cells by surface-bound organisms.
Ig heavy chain protein controls B cell development by regulating germ-line transcription and retargeting V(D)J recombination.
Authors: Schlissel M S , Morrow T 
Published: December 2022

Abstract
The membrane-associated form of Ig heavy chain (mu) protein has been implicated as a critical regulator of B cell development. Mutant mice unable to produce the membrane form of mu protein fail to produce mature B cells. Splenic B cells from mice transgenic for a functionally rearranged Ig mu gene show a marked decrease in endogenous heavy chain gene rearrangement. We have analyzed the effects of a human mu transgene on the regulation of V(D)J recombination during B cell development in the mouse fetal liver. We found that mu transgenic and wild-type littermate mice begin kappa light chain gene rearrangement at the same time during development but the transgenic mice show a striking increase in the frequency of kappa gene rearrangement. The transgenic mice also show an increase in the levels of a germ-line kappa gene transcript known to be associated with kappa gene rearrangement. D-to-JH heavy chain gene rearrangement is unaffected throughout development by the presence of the mu transgene. Endogenous heavy chain gene V-to-DJH rearrangement occurs with similar frequency in transgenic and nontransgenic fetal livers during midgestation but is reduced in late gestation mu transgenic fetal liver. We show that this decrease in rearrangement is associated with a decrease in unrearranged VH gene transcription. Furthermore, we show that changes in the frequencies of rearranged kappa and mu genes are accompanied by changes in the frequencies of dsDNA breaks, a V(D)J recombination reaction intermediate associated with each of these loci. We propose that membrane-associated mu protein regulates B cell development by signaling a change in the pattern of unrearranged Ig gene transcriptional activity, thereby retargeting the V(D)J recombinase.
Identification and characterization of IL-2 hyper-responsive NZB/WF1 CD5- B cells.
Authors: Hirose S , Nakanishi K , Yoshimoto T , Kashiwamura S , Hiroishi K , Matsumoto H , Hamaoka T , Shinka S , Higashino K 
Published: December 2022

Abstract
The responsiveness of CD5- and CD5+ B cells of BALB/c and NZB/WF1 mice to various cytokines was examined with respect to their growth and differentiation. BALB/c splenic CD5- B cells required longer incubation with IL-2 or pretreatment with IL-4 to respond to IL-2 by DNA synthesis, whereas NZB/WF1 CD5- B cells were highly competent to IL-2. Flow cytometric analysis demonstrated that NZB/WF1 and BALB/c CD5- B cells had higher and intermediate proportions of B cells positive for IL-2R beta, respectively. On the other hand, BALB/c and NZB/WF1 splenic CD5+ B cells consisted of lower proportion of B cells positive for IL-2R beta than did their corresponding CD5- B cells and grew meagerly in response to IL-2. Peritoneal exudative CD5+ B cells of NZB/WF1 mice lacked IL-2R beta mRNA expression and failed to respond to IL-2. Although both BALB/c and NZB/WF1 CD5- B cells pretreated with anti-IgM, IL-4, and IL-5 responded to IL-2 by DNA synthesis, only BALB/c CD5- B cells developed into IgM-producing cells. Furthermore, BALB/c, but not NZB/WF1 CD5-, B cells pretreated with anti-IgM and IL-5 responded to IL-2 by IgM production without DNA synthesis. Thus, cross-talk between IL-4 and IL-2 operated in the growth responses of both BALB/c and NZB/WF1 splenic CD5- B cells, whereas cross-talk between IL-5 and IL-2 operated only in the differentiation of BALB/c CD5- B cells, providing us with another intriguing functional abnormality of NZB/WF1 B cells.
Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates.
Authors: Lehner T , Bergmeier L A , Tao L , Panagiotidi C , Klavinskis L S , Hussain L , Ward R G , Meyers N , Adams S E , Gearing A J 
Published: December 2022

Abstract
A s.c. route of immunization was developed in non-human primates, which targets the genitourinary-rectal associated lymphoid tissue. A vaccine consisting of rSIV gag p27, expressed as hybrid Ty virus-like particles (p27: Ty-VLP) was administered in the proximity of the internal iliac lymph nodes. Secretory IgA and IgG Abs to the p27 Ag were elicited in the vaginal, male urethral, rectal and seminal fluids, urine and serum. Two or more immunodominant B cell epitopes were identified within peptides 51-90 and 121-170 of the sequence of p27, using serum or biliary IgA and IgG Abs. CD4+ T cell proliferative responses to p27 were elicited predominantly in the targeted internal iliac, as well as the inferior mesenteric lymph nodes and the spleen, but not in the unrelated lymph nodes. These cells were then studied for helper function in p27 specific B cell Ab synthesis. Specific IgA and IgG Abs were detected in the same lymphoid tissues as those that displayed proliferative responses. However, cross-over reconstitution experiments between splenic and iliac lymph node B and CD4+ T cells suggest that the iliac B cells are essential for specific IgA Ab synthesis, whereas splenic B cells preferentially synthesize IgG Ab. The targeted lymph node (TLN) route of immunization gave comparable B cell, proliferative T cell, and Th cell responses to the vaginal, male genitourinary, and rectal mucosal routes, which were augmented by oral immunization. However, the TLN route induced urinary and seminal fluid sIgA and IgG Abs in addition to genital and rectal Abs. Generating secretory IgA and IgG Abs at the mucosal surfaces, and T and B cell immunity in the regional draining lymph nodes, spleen and circulation by TLN immunization may prevent transmission of virus through the mucosa, dissemination of the virus, and the formation of a latent reservoir of infection.
Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity in MRL-lpr/lpr mice.
Authors: Shirai A , Aoki I , Otani M , Mond J J , Klinman D M 
Published: December 2022

Abstract
The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production.
Epstein-Barr virus induces actin polymerization in human B cells.
Authors: Melamed I , Stein L , Roifman C M 
Published: December 2022

Abstract
The EBV selectively infects human and primate lymphocytes. This selective tropism occurs as a result of live virus infection through permissive membrane receptors. Once EBV has entered the cell, it induces proliferation and immortalization of these cells. The mechanism of EBV infection, however, remains largely unknown. We demonstrate here that a transforming strain, but not a nontransforming strain, of EBV stimulates the conversion of globular actin (G-actin) to filamentous actin (F-actin), a process that has been associated with activation and transformation of other cell types. Preincubation of B cells with botulinum C2 toxin or cytochalasin, which block the conversion of G-actin to F-actin, resulted in the inhibition of EBV-induced proliferation. These findings indicate that actin rearrangement is essential for infection of B cells by EBV.
CD1+ human thymocytes proliferate in response to superantigen staphylococcal enterotoxin B1.
Authors: Todd S C , Baccala R , Hedrick J A , Theofilopoulos A N , Tsoukas C D 
Published: December 2022

Abstract
Exposure of human thymocytes to superantigens results in the deletion of thymocytes expressing specific TCR-V beta genes. The factors that contribute to this deletion may relate to the inherent nature of the T cell at a given stage of development. In this paper, we demonstrate that CD1+ human cortical thymocytes are capable of proliferating in response to a bacterial superantigen (staphylococcal enterotoxin B (SEB)) in the presence of autologous CD2-/low thymic APCs. Phenotypic analysis of the responding populations revealed that the majority of the CD1+ cells were CD4+CD8low or CD8+CD4low cells. The response is triggered by low concentrations of SEB, requires the participation of the TCR and IL-2R molecules, and is inhibited by cyclosporin A. Thymocytes that express specific V beta genes are expanded, which results in an engagement profile that parallels that found in PBLs. Additionally, four V beta-chains that have not been reported previously are shown to engage SEB. Once stimulated, the thymocytes failed to respond to additional SEB; however, they could be induced to proliferative with IL-2, which suggests that these expanded populations had become anergic. These data represent the first demonstration of a human cortical thymocyte subpopulation that responds to superantigen by proliferation and subsequent anergy.
Effect of aging on murine macrophages. Diminished response to IFN-gamma for enhanced oxidative metabolism.
Authors: Ding A , Hwang S , Schwab R 
Published: December 2022

Abstract
The ability of macrophages to secrete reactive oxygen intermediates, as well as reactive nitrogen intermediates, correlates closely with their capacity to perform two critical effector functions: intracellular killing of microorganisms and lysis of tumor cells. In this study, age-associated changes in the ability of caseinate-elicited peritoneal macrophages to release hydrogen peroxide were determined. Macrophages from aged BALB/c mice produced 50% less hydrogen peroxide than those from young mice in response to PMA or opsonized zymosan. In contrast, the production of macrophage-activating cytokines including IFN-gamma was not diminished in splenocyte supernatants from the aged group. Furthermore, no difference was detected in surface expression of IFN-gamma receptor in old and young mice. Macrophage responses to IFN-gamma, however, declined with aging. In vitro, IFN-gamma-induced release of hydrogen peroxide and nitric oxide was 50% lower in old mice than in young mice. IFN-gamma-induced tyrosine phosphorylation of MAPK, an early activation event, was undetectable in macrophages from the aged mice. These data demonstrate that diminished responses of macrophages to activating signals are one aspect of the impaired immune response in aged mice.
Natural autoantibody against apolipoprotein A-I. Detection and characterization of the monoclonal antibody established from normal unimmunized BALB/c mice.
Authors: Imai H , Suzuki S , Uchida K , Kikuchi K , Sugiyama H , Kohno H , Umeda M , Inoue K 
Published: December 2022

Abstract
During the course of studying the immunogenicity of soybean lipids, we observed frequent production of the mAbs that bind to apolipoprotein A-I (apoA-I) when spleen cells from unimmunized normal BALB/c mice were employed for fusion. Of the 986 colonies from six fusions, 38 (3.9% of the total) were directed against apoA-I and 13 mAbs (IgM) were established for further analysis. The following lines of evidence indicate that this family of mAb may form a novel family of natural autoantibodies against apoA-I: 1) The mAbs were shown to bind effectively to high density lipoprotein from various species, including BALB/c mouse, and immunoblotting analyses revealed that the mAbs bound specifically to the 28-kDa protein of high density lipoprotein. 2) The 28-kDa protein was purified to homogeneity and identified as apoA-I by amino acid sequence analyses and by its cross-reactivity with a xenogenic anti-apoA-I mAb (clone A/11). 3) Differing from the xenogenic anti-apoA-I mAb, the present mAb did not bind to native apoA-I, whereas an effective binding was observed only when the apoA-I had formed a complex with neutral lipids containing polyunsaturated fatty acids such as trilinoleoylglycerol and 5-cholesten-3 beta-ol 3-linoleate. 4) Sera from unimmunized BALB/c mice had readily detectable Abs against apoA-I and the majority of the serum autoantibodies were of the IgA and IgM isotype. 5) The anti-apoA-I mAbs displayed a functional heterogeneity in their reactivity with polyanionic substances and some of the mAbs established showed an extensive cross-reaction with polyanionic substances such as ssDNA and cardiolipin.