bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligoclonality of lung T lymphocytes following exposure to allergen in asthma.
Authors: Burastero S E , Crimi E , Balbo A , Vavassori M , Borgonovo B , Gaffi D , Frittoli E , Casorati G , Rossi G A 
Published: December 2022

Abstract
We were interested in studying the lung allergen-specific T cell repertoire in different conditions of allergen exposure in subjects with atopic asthma. Twenty-one allergic individuals were studied: 17 subjects suffering mainly from asthma and 4 from rhinitis. They all performed spirometry and methacholine challenge. All patients were subjected to bronchoalveolar lavage (BAL), either at base line (no challenge) or after allergen or histamine challenge, and the TCR repertoire of their lung T cells was studied with heteroduplex analysis. Expansion of single T cell clones was observed in one (of seven) asthmatic subject that reported a recent exposure to allergen and had high bronchial hypersensitivity to methacholine, and in seven/seven asthmatic subjects who underwent BAL after they suffered an early asthmatic reaction to experimental allergen inhalation. Remarkably, ex vivo expanded clones included allergen-specific T cells. In two of the seven subjects who underwent BAL after allergen challenge, two different lung segments were lavaged. A strikingly symmetrical distribution of the expanded clones was found in these samples. Control subjects and six of seven asthmatic patients studied at base line showed polyclonality of lung T cells. In conclusion, T lymphocytes are clonally expanded in the lower respiratory tract only in asthmatic subjects exposed to allergen. These results suggest that in allergic asthma, the inhalation of sensitizing allergens can recruit to the lung T lymphocytes that include allergen-specific T cell clones.
Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis. Secondary role of iodination.
Authors: Kong Y C , McCormick D J , Wan Q , Motte R W , Fuller B E , Giraldo A A , David C S 
Published: December 2022

Abstract
We hypothesized earlier that conserved T cell epitopes and those unique to mouse thyroglobulin (MTg) contributed to its total thyroiditogenicity in murine autoimmune thyroiditis. Recent studies of synthetic peptides from human Tg (HTg) revealed no immunodominant epitopes. The role of iodine residues, considered by some to render Tg immunogenic, became unclear, since only one 12-mer peptide contained thyroxine (T4) positioned at hormonogenic site 2553. It primed T cells for thyroiditis transfer, but noniodinated peptide containing thyronine (T0) was not compared. To determine 1) whether other primary hormonogenic sites were likewise immunogenic and 2) whether iodination was requisite for this and other sites to be an autoepitope, we derivatized three pairs of 12-mer peptides, 1-12, 2549-2560, 2559-2570, containing T0 or T4 at positions 5, 2553, or 2567, respectively. The six peptides were used to stimulate MTg-primed cells in vitro and to immunize mice. None directly induced thyroiditis; peptide Abs were the lowest in mice given hT0(2567) or hT4(2567). Of the three T4-containing peptides, hT4(5) and hT4(2553), but not hT4(2567), stimulated MTg-primed or HTg-primed T cells in vitro, with hT4(2553) being the stronger. Comparing hT0(2553) with hT4(2553), both activated MTg-primed, or peptide-primed, T cells to transfer thyroiditis. The marked immunogenicity of noniodinated hT0(2553) and the poor antigenicity of hT4(5) and hT4(2567) demonstrate that immunogenicity of a conserved hormonogenic site is dependent more on its amino acid sequence than on T4 substitution. Iodination may enhance antigenicity and/or binding affinity, but it is not required for a Tg hormonogenic site to be an autoepitope.
Antiviral cytotoxic T lymphocytes in vaginal mucosa of simian immunodeficiency virus-infected rhesus macaques.
Authors: Lohman B L , Miller C J , McChesney M B 
Published: December 2022

Abstract
The mucosal immune system of the female reproductive tract is of central importance for protection against sexually transmitted diseases, including HIV; however, this arm of the immune system remains poorly understood. Antiviral CTL responses never have been documented in the genital tract and the role of CTL in this anatomic site is unknown. In this study, CD8+ intraepithelial lymphocytes (IEL) in the vaginas of six simian immunodeficiency virus (SIV)-infected female rhesus macaques were identified by immunohistochemistry to be CD2+ and TCR beta-chain+. In addition, the majority of CD8+ IEL contained TIA-1+ cytoplasmic granules that are associated with CTL activity. CD8+ T cells were isolated from the vaginal epithelium and submucosa and amplified by limiting dilution in the presence of feeder cells. SIV p55gag and/or gp160env-specific lysis was detected in cultures of vaginal epithelial but not submucosal CD8+ T lymphocytes. Estimated SIV-specific precursor CTL frequencies were higher in the vaginal CD8+ IEL population of chronically infected monkeys than in the same cells from acutely infected monkeys or a naive control monkey. These results provide the first demonstration that antiviral CTL are present in the vaginal epithelium, and suggest that a vaccine may be able to generate anti-HIV CTL in the genital mucosa.
Myelin antigen-coupled splenocytes suppress experimental autoimmune encephalomyelitis in Lewis rats through a partially reversible anergy mechanism.
Authors: Vandenbark A A , Celnik B , Vainiene M , Miller S D , Offner H 
Published: December 2022

Abstract
Mechanisms of adult tolerance induced by injecting myelin Ag/ECDI (ethyl carbodiimide)-coupled splenocytes (Ag-SPL) were evaluated in Lewis rat experimental autoimmune encephalomyelitis (EAE). Rats could be tolerized against the major encephalitogenic epitope of guinea pig basic protein (Gp-BP), residues 72-89, using either S72-89-SPL or crude spinal cord homogenate (SCH)-SPL. In contrast to lymph node responses that were not affected significantly, the proliferation responses of blood T cells were markedly inhibited at the peak of EAE and during the recovery period to both Gp-BP and S72-89, but not to purified protein derivative (PPD), demonstrating Ag-specific tolerance. Tolerance induction reduced the number of infiltrating spinal cord (SC) cells, especially recruited CD45RC+ cells, as well as SC proliferation responses to S72-89 throughout the course of EAE. In contrast, SC response to PPD was increased at onset of EAE, but later during recovery the PPD response was also decreased compared with control rats. Tolerance induced by S72-89-SPL in blood and SC T cells could be reversed by incubation in IL-2, in accordance with an anergy model. BP-specific T cells preincubated in vitro with Gp-BP-SPL were rendered unresponsive to Gp-BP or S72-89, compared with the same T cells preincubated with histone (Hist)-SPL that remained Ag responsive. Consistent with an anergy model, preincubation with BP-SPL+IL-2 partially prevented tolerance induction to BP. T cells tolerized in vitro to BP-SPL induced milder EAE with delayed onset compared with control-tolerized T cells that produced lethal disease. These results demonstrate the efficacy of myelin Ag-coupled SPL in preventing EAE by selective tolerization of encephalitogenic T cells through a partially reversible anergy-induction mechanism.
CD38 signal transduction in human B cell precursors. Rapid induction of tyrosine phosphorylation, activation of syk tyrosine kinase, and phosphorylation of phospholipase C-gamma and phosphatidylinositol 3-kinase.
Authors: Silvennoinen O , Nishigaki H , Kitanaka A , Kumagai M , Ito C , Malavasi F , Lin Q , Conley M E , Campana D 
Published: December 2022

Abstract
Ligation of CD38 inhibits proliferation and induces apoptosis of human immature B cells, but the molecular mechanisms underlying this function are unknown. We found that CD38 dimerization with the specific mAbs T16 and IB4 induces rapid and transient tyrosine phosphorylation of several intracellular proteins in the immature B cell lines RS4;11, REH, 380, Nalm6, and OP-1. This effect could be markedly reduced by incubating cells with the tyrosine kinase inhibitors genistein, staurosporine, and herbimycin A. CD38 dimerization induced tyrosine phosphorylation of the protein kinase syk and increased syk kinase activity. CD38 dimerization also induced tyrosine phosphorylation of phospholipase C-gamma and of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K). The latter was accompanied by a distinct increase in PI 3-kinase activity in the immunoprecipitates obtained with an anti-phosphotyrosine Ab. In contrast to the signaling triggered by surface Ig engagement in B lymphocytes, CD38 ligation did not appear to induce tyrosine phosphorylation of the src-like protein tyrosine kinases lyn, fyn, and btk, or of vav- and ras-GTPase-activating protein, nor did it induce detectable changes in cytosolic CA2+ concentrations. CD38 signaling also differed from cytokine-induced signaling in that it did not cause tyrosine phosphorylation of Jak1 and Jak2. Finally, CD38 ligation did not inhibit IL-3-induced tyrosine phosphorylation of Jak2. These results identify CD38 as a cell surface receptor with signal transduction properties activated by dimerization. Induction of signal transduction by CD38 ligation implies the existence of a yet unidentified natural ligand of CD38.
Identification of a population of CD4+ CTL that utilizes a perforin- rather than a Fas ligand-dependent cytotoxic mechanism.
Authors: Williams N S , Engelhard V H 
Published: December 2022

Abstract
Although cytotoxic activity has generally been shown to reside in the CD8+ population of T lymphocytes, there are numerous examples of cytotoxic CD4+ T cells. In the present study, we found that after depletion of CD8+ T cells, CD4+ T cells cultured in short-term in vitro mixed lymphocyte cultures developed strong Ag-specific cytotoxic activity. Such CD4+ CTL lysed both Fas+ and Fas- target cells and developed in Fas ligand-deficient gld mice. Thus, in contrast to several recent reports involving long-term T cell clones or short-term mitogen-activated splenocytes, the cytotoxic activity of these CD4+ CTL is not dependent on Fas-Fas ligand interactions. However, CD4+ cells derived in a similar manner from perforin knockout mice showed greatly decreased target cell lysis, indicating that their cytotoxic activity is primarily dependent on a perforin-based mechanism. The Fas-Fas ligand pathway has been shown to be important in the maintenance of peripheral tolerance, but to have a minimal role in protection against viral and bacterial pathogens. Thus, the existence of a population of CD4+ CTL that utilizes perforin re-emphasizes the likely importance of these cells in a classical defensive role against foreign pathogens, in addition to their already implied role as modulators of the immune response.
Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen.
Authors: Chen P W , Wang M , Bronte V , Zhai Y , Rosenberg S A , Restifo N P 
Published: December 2022

Abstract
Recombinant adenovirus (rAd), deleted of critical genes that enable viral replication and replaced with genes encoding heterologous proteins, has been shown to be a safe and effective vector in gene therapy studies. To evaluate a potential role for rAd as an immunogen, we used two different replication-defective type 2 rAds encoding the model Ag, beta-galactosidase (beta-gal). To determine whether rAd elicited the kind of immune responses therapeutic in an anti-tumor setting, the beta-gal-expressing adenocarcinoma, CT26.CL25, was used. Splenocytes from BALB/c mice immunized with 1 x 10(7) infectious units (iu) of rAd demonstrated anti-beta-gal activity after in vitro culture with the relevant L(d) beta-gal peptide. Adoptive transfer of these same splenocytes produced dramatic regression of established pulmonary metastases. However, when tumor-bearing mice were treated with 1 x 10(7) iu of rAd, no reduction in established disease was observed even when rAd was given with exogenous IL-2. To increase the viral dose delivered to each animal, we used an E1-E4-deleted rAd that could be grown to much higher titers. Significant reduction occurred with 10-fold more rAd (1 x10(8) iu) was administered. Exogenous IL-2 administration with 1 x 10(8) iu of rAd resulted in augmentation of this anti-tumor effect. These findings demonstrate that when using a nonreplicating virus, the viral dose is directly related to the immune response generated. These data constitute the first reported use of rAd in the treatment of an established experimental cancer and may have implication for the treatment of human cancer.
Secretion of IL-16 (lymphocyte chemoattractant factor) from serotonin-stimulated CD8+ T cells in vitro.
Authors: Laberge S , Cruikshank W W , Beer D J , Center D M 
Published: December 2022

Abstract
At sites of inflammation, mononuclear cells are in close contact with aggregated platelets. Although the physiologic role of this association is not clear, this proximity suggests that platelet-derived mediators may play a role in chemoattraction of T lymphocytes. In the current study we investigated serotonin receptor-bearing lymphocyte modulation of T cell migration. Serotonin-stimulated human blood mononuclear cells secrete lymphocyte chemoattractant activity with selective activity for CD4+ T cells. This chemoattractant activity was observed within 2 h of exposure to serotonin and was blocked by serotonin type 2 receptor antagonists. Molecular sieve chromatography of supernatant from serotonin-stimulated PBMCs revealed a single peak of T cell chemoattractant activity with an apparent molecular mass of 56 kDa and a pl of 9.1. Neutralizing experiments with specific mAbs indicated that the serotonin-induced chemotactic factor was the previously characterized lymphocyte chemoattractant factor (LCF), recently designated IL-16. Serotonin induced secretion of IL-16 from CD8+, not CD4+, T cells which did not require the de novo protein synthesis. These studies suggest that serotonin, via serotonin type 2 receptors, may promote the recruitment of CD4+ T lymphocytes into an inflammatory focus.
Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release.
Authors: Loetscher P , Seitz M , Clark-Lewis I , Baggiolini M , Moser B 
Published: December 2022

Abstract
The responses of cloned human NK cells (ERNK57) to seven CC chemokines (monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and 1309) and two CXC chemokines (IL-8 and IP-10) were studied. Except for 1309, all CC chemokines induced chemotaxis of the NK cells in vitro, whereas the CXC chemokines were inactive. Maximal activity was obtained at 1 nM for MCP-1 and 10 to 100 nM for the other CC chemokines. The response showed a typically bimodal concentration dependence in all cases, except for RANTES, which induced a linear increase of migration over the concentration range of 0.1 to 1000 nM. A transient rise of the cytosolic-free Ca2+ concentration ([Ca2+]i), which is characteristic for chemokine-stimulated leukocytes, was observed in NK cells after stimulation with all six active chemokines. Since granule exocytosis is required for NK cell-dependent target killing, the effect of CC chemokines on exocytosis was tested. All CC chemokines that induced chemotaxis and [Ca2+]i changes also induced the release of granzyme A and N-acetyl-beta-D-glucosaminidase from cloned and blood NK cells, as well as CD8+ T cells after pretreatment with cytochalasin B. Maximum release was obtained from NK cells, and amounted to 35% and 13% of the total content of granzyme A and N-acetyl-beta-D-glucosaminidase, respectively. The capacity of cloned NK cells and CD8+ T cells to respond to chemokines depended on the time in culture after stimulation with PHA in the presence of irradiated feeder cells, and maximum responses were observed after 10 to 16 days. Our results demonstrate that CC chemokines activate NK cells, and are, therefore, not only attractants for monocytes, T lymphocytes, and eosinophil and basophil granulocytes.
Activated alpha beta-CD8+, but not alpha alpha-CD8+, TCR-alpha beta+ murine intestinal intraepithelial lymphocytes can mediate perforin-based cytotoxicity, whereas both subsets are active in Fas-based cytotoxicity.
Authors: Gelfanov V , Gelfanova V , Lai Y G , Liao N S 
Published: December 2022

Abstract
CD8 single-positive (CD8+) T cells in murine intestinal intraepithelial lymphocytes (iIEL) consist of alpha alpha-CD8+ and alpha beta-CD8+ subpopulations. Cytotoxicity represents an important function of peripheral CD8+ T cells, so we examined perforin-granzymebased and Fas-based cytotoxicity of activated CD8+ TCR-alpha beta+ iIEL subsets. We found that allospecific CTL activity was induced from alpha beta-CD8+ iIEL but not from alpha alpha-CD8+ iIEL even when allospecific TCR were present on the iIEL, as demonstrated by using 2C TCR transgenic mice. On the other hand, both CD8+ iIEL subsets proliferated upon allostimulation with a lower responder frequency than CD8+ LN cells. The alpha alpha-CD8+ TCR-alpha beta+ iIEL appeared to lose their ability to perform perforin-based killing after activation through TCR because fresh cells lysed P815 cells coated with anti-TCR beta-chain (TCR-beta) mAb, whereas cells activated by plate-bound anti-TCR mAb did not. Of interest, both activated CD8+ TCR-alpha beta+ iIEL subsets, but not fresh cells, were able to mediate Fas-based killing when triggered with PMA and CA2+ ionophore.
Specific Th1 cytokine down-regulation associated with primary clinically derived human immunodeficiency virus type 1 Nef gene-induced expression.
Authors: Collette Y , Chang H L , Cerdan C , Chambost H , Algarte M , Mawas C , Imbert J , Burny A , Olive D 
Published: December 2022

Abstract
HIV-1 infection is associated with a progressive and functional decline in the CD4+ lymphoid Th1 subset. Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine production. By use of a T cell-specific inducible expression system, we show that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, whereas IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffected. In addition to this, independent transfected clones expressing various nef genes, including nef sequences amplified directly from an HIV-1 primary clinical isolate, displayed a similar pattern of cytokine expression. The specific Th1 impairment induced by nef, therefore, seems to be an important and conserved feature of HIV-1 infection and may represent a significant function of this viral gene in AIDS pathogenesis.
TCR in Fas-sensitive T cells from labial salivary glands of patients with Sjögren's syndrome.
Authors: Sumida T , Matsumoto I , Murata H , Namekawa T , Matsumura R , Tomioka H , Iwamoto I , Saito Y , Mizushima Y , Hasunuma T , Maeda T , Nishioka K 
Published: December 2022

Abstract
Apoptosis is found in labial salivary glands of patients with Sjogren's syndrome (SS). To analyze the pathogenesis of apoptosis in labial salivary glands of SS patients, we examined the expression of Fas Ag and Fas ligand (FasL) and TCR on T cells susceptible to anti-Fas mAbs (CH-11). Fas Ag is expressed on epithelial cells and mononuclear cells in the salivary glands as observed by an immunohistochemical method. FasL is over-expressed specifically on T cells infiltrating into the labial salivary glands as seen by an reverse transcription-PCR method. These results suggest that apoptosis in SS lips is mediated by a Fas/FasL pathway. PCR single-strand conformation polymorphism (SSCP) clearly demonstrated that more than 40% of the T cells accumulated in labial salivary glands are deleted by incubation with CH-11 for 24 h in vitro, indicating that these expanded cells are Fas sensitive. junctional sequence analysis showed that the same conserved amino acid motifs (LAGG, RLA, SLG, QGPG, PGG, GGE, RGR, KPG, AGD, and MLG) in complementarity determining region 3 (CDR3) are found in Fas-sensitive T cell clones, whereas they are not detected in Fas-resistant clones, suggesting that Fas-sensitive T cells recognize restricted T cell epitopes on autoantigens. In conclusion, the findings suggest that Fas-sensitive T cells in labial salivary glands of SS patients are generated by Ag stimulation and might function as autoreactive T cells.
Are transporter associated with antigen processing (TAP) and tapasin class I MHC chaperones?
Authors: Solheim J C , Carreno B M , Hansen T H 
Published: December 2022

Abstract
Class I MHC heavy chains associate with many proteins in the endoplasmic reticulum, including TAP, calnexin, calreticulin, and the newly defined tapasin molecule. Recent studies have begun to resolve the nature of how these proteins interact with class I as well as the functional significance of each of these interactions. We propose here that TAP and tapasin are leading candidates to be highly specific chaperones for the class I molecule.
Costimulation of CD28- T lymphocytes by 4-1BB ligand.
Authors: DeBenedette M A , Shahinian A , Mak T W , Watts T H 
Published: December 2022

Abstract
The interaction of the T cell surface protein CD28 with its ligand, B7-1 or B7-2, provides a critical costimulatory signal for T cell activation. T cells from CD28- mice are deficient in a variety of responses, including those to lectins and allogeneic spleen cells. However, some immune responses do occur in CD28- mice, suggesting the existence of alternate costimulatory pathways. In this work, we show that T cells purified from CD28- mice respond to B lymphomas expressing 4-1BB ligand (4-1BBL), a member of the TNF gene family. This response is inhibited by a soluble form of 4-1BB, the T cell surface receptor for 4-1BBL. Thus, 4-1BBL/4-1BB interaction provides costimulatory signals to T cells independent of signaling through the CD28 receptor. We find that 4-1BBL is inducible on splenic B cells by CD40 ligand/CD40 interaction or by culturing of splenic dendritic cells, treatments that also induce B7 family molecules. CD28- T cells fail to respond in an MLR to resting allogeneic spleen cells. However, treatment of spleen cells with CD40 ligand renders them competent in activation of CD28- T cells. In contrast to results using B lymphomas as APC, soluble 4-1BB fails to inhibit the T cell response to activated spleen cells. This failure of soluble 4-1BB to block an MLR between CD28+ or CD28- T cells and allogeneic spleen cells is in contrast to a previous report with CD28+ cells.