bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of MHC-unrestricted cytolytic CD4+ T cells against virally infected target cells by cross-linking CD4 molecules.
Authors: Choi S H , Splitter G A 
Published: December 2022

Abstract
Cross-linking CD4 molecules with the use of specific mAbs induced Ag-nonspecific, MHC-unrestricted killing by human or bovine CD4+ T cells and human allospecific T cell clones against virally infected (bovine herpesvirus-1 and herpes simplex virus-1) target cells. Heat-aggregated goat IgG anti-mouse IgG elevated CD4 cross-linking efficiency, resulting in augmented killing activity by effector cells. However, Ab-activated effector cells failed to kill tumor target cell lines, e.g., K562, Daudi (human), and BL3 (bovine). The result supports the hypotheses that the CD4 molecule plays an important role in activating CD4 cytotoxic cells and that viral glycoproteins participate in conjugating target cells with activated effector cells in two species. The herpesviruses eliciting killing represent potential natural infections for each species. The relationship between a cytolytic response and cell proliferation was independent because cross-linking of CD4 molecules induced cytotoxicity but not T cell proliferation, in contrast to cross-linking CD3 molecules. Our findings of non-MHC-restricted cytotoxic lymphocytes induced by cross-linking CD4 molecules identify an activation mechanism of antiviral cytotoxicity.
TCR usage and functional capabilities of human gamma delta T cells at birth.
Authors: Morita C T , Parker C M , Brenner M B , Band H 
Published: December 2022

Abstract
Little is known about the gamma delta T cells in human neonatal umbilical cord blood. To compare neonatal cord blood and adult blood gamma delta T cells, we studied the V gamma and V delta gene segment usage in these populations by flow cytometry, and we derived cord blood gamma delta T cell clones to determine their functional capabilities. Unlike adult blood gamma delta T cells that predominantly express V gamma 2V delta 2 TCRs, neonatal cord blood gamma delta T cells expressed diverse V gamma and V delta gene segments paired in a variety of combinations rarely observed in adults. gamma delta T cell clones derived from neonatal cord blood similarly expressed a diverse array of TCRs. These cord blood-derived gamma delta T cell clones had weak cytolytic activity when assayed for K562 tumor cell killing, lectin-mediated cytolysis, and redirected cytolysis. They also expressed lower levels of the CD2, LFA-1, and CD45RO cell surface receptors as compared with strongly cytolytic adult gamma delta T cell clones. These properties of the cord blood-derived gamma delta T cell clones, weak cytotoxic activity and low adhesion molecule expression, were similar to the properties of the CD4+ subset of adult gamma delta T cells. Thus, neonatal gamma delta T cells are functionally different from the majority of adult gamma delta T cells and display a distinct TCR repertoire and accessory molecule profile.
IL-12 stimulates the development of acute graft-versus-host disease in mice that normally would develop chronic, autoimmune graft-versus-host disease.
Authors: Via C S , Rus V , Gately M K , Finkelman F D 
Published: December 2022

Abstract
The injection of DBA/2 (D2) spleen cells into (C57BL/6 x DBA/2)F1 mice (BDF1) induces a chronic, autoimmune graft-vs-host disease (GVHD) that is characterized by: increased production of Th2-associated cytokines; increased levels of serum Ig, including IgE; increased production of IgG anti-DNA Abs; and no detectable antihost CTL activity. Experiments were performed to determine if treatment with the cytokine IL-12, which stimulates the production of Th1-associated cytokines and inhibits Th2-associated cytokine production, would inhibit humoral autoimmunity in this system. Treatment of mice with 100 ng IL-12 per day for 5 days, starting on the day of cell transfer, resulted in: 1) near complete suppression of autoantibody production; 2) decreased serum Ig levels; 3) detectable donor antihost CTL activity; and 4) greatly reduced numbers of host splenic B and T cells. Treatment of mice with a neutralizing anti-IFN-gamma mAb did not reverse these effects of IL-12. Thirty nanograms per day resulted in reduced numbers of host B cells and reduced serum anti-DNA levels, but no detectable antihost CTL activity. IL-12 treatment initiated 7 days after cell transfer had little effect on the development of autoimmune GVHD. These observations suggest the following: 1) IL-12 inhibits humoral autoimmunity in a murine parent--&gt;F1 GVHD model by inducing the activation of host-reactive CTLs that reject the host immune system. 2) This effect is IFN-gamma-independent. 3) IL-12 needs to be present during the initial differentiation of T cells in this system to have this effect.
Topology of the loxoribine binding site. Studies with inactive loxoribine analogues.
Authors: Goodman M G , Goodman J H 
Published: December 2022

Abstract
We have previously described a class of immunostimulatory ribonucleoside, exemplified by loxoribine (7-allyl-8-oxoguanosine) and 8-bromoguanosine, that act on cycling B cells to promote nonspecific proliferation and differention, and that synergize with Ag to recruit quiescent Ag-reactive B cells to undergo differentiation and high level Ab production. In murine B cells, two distinct binding activities have been characterized that have dissociation constants that parallel their distinctive dose-response profiles. The SJL mouse strain, which is hypo-responsive to the B cell proliferative properties of these molecules, exhibits a dissociation constant of 10- to 20-fold lower affinity than that of normal murine strains; its Kd for the higher affinity-binding interaction, however, is essentially normal. These observations suggested the existence of two distinct binding activities. Recently, immunoselective subgroups of loxoribine have been described, with an ability to stimulate individual components of the immune response that correlates with specific changes in discrete domains of the nucleoside molecule. By using a panel of nonstimulatory loxoribine analogues as inhibitors, we now report further evidence for the existence of unique sites on loxoribine binding proteins that recognize distinct domains on nucleoside analogues; changes in these regions confer immunologic selectivity. These data confirm the conclusions of previous studies, extend our understanding of the topology of subsites that are otherwise silent, and provide insight into the binding site mediating adjuvanticity. These results allow more profound appreciation of the nature of structural changes that will permit a tighter fit between ligand and binding site, ultimately promoting the design of more potent immunoselective agents.
Murine VCAM-1. Molecular cloning, mapping, and analysis of a truncated form.
Authors: Kumar A G , Dai X Y , Kozak C A , Mims M P , Gotto A M , Ballantyne C M 
Published: December 2022

Abstract
Vascular cell adhesion molecule-1 (VCAM-1) is a member of the Ig superfamily that shows increased expression in a number of pathologic conditions. The role of VCAM-1 in human disease remains undefined and murine models are being extensively studied to help define the importance of VCAM-1 in inflammatory disorders. We have cloned and characterized the murine Vcam1 gene including 3 kb of 5'-flanking sequences and mapped the gene to chromosome 3 near Amy1. cDNA clones isolated from a stimulated hepatic library were found to encode a truncated form of VCAM-1 (T-VCAM-1) which contains Ig domains 1 through 3 and has a unique alternative carboxyl terminus. This form arises by alternative splicing. High level expression of T-VCAM-1 in transfected L cells was sufficient to support adhesion of lymphocytes, and this adhesion was blocked by Abs to VCAM-1. Treatment of transfected COS cells with phospholipase C led to reduced levels of T-VCAM-1 on the cell surface consistent with glycosylphosphatidylinositol linkage. Northern blot analysis showed that mRNA for T-VCAM-1 is inducible in multiple tissues after stimulation with endotoxin. Both forms of VCAM-1 were expressed in cultured endothelial, fibroblast, and aortic smooth muscle cells, whereas neither form was observed in monocyte- and lymphocyte-derived lines. Differential regulation of both forms of VCAM-1 was observed in the three different cell types that are present in the vessel wall. Thus, expression of VCAM-1 is restricted and controlled at the level of transcription and by alternative splicing.
Elicitation of specific cytotoxic T cells by immunization with malaria soluble synthetic polypeptides.
Authors: Blum-Tirouvanziam U , Beghdadi-Rais C , Roggero M A , Valmori D , Bertholet S , Bron C , Fasel N , Corradin G 
Published: December 2022

Abstract
We have studied the immunogenicity of Plasmodium falciparum circumsporozoite (CS) protein-derived synthetic polypeptides in mice. These synthetic peptides correspond to the N- and the C-terminal domains 22-125 and 289-390, respectively of the P. falciparum 7G8 isolate CS protein expressed on the sporozoite surface. They comprise what is believed to be the mature protein, except for the central repetitive B cell domain. BALB/c (H-2d) mice were immunized s.c. with 50 micrograms soluble CS polypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resultant CTLs obtained by in vitro restimulation of primed lymph node (LN) cells recognized H-2Kd target cells in the presence of short synthetic peptides defined in the present study. These epitopes are contained within the N- and C-terminal regions of the CS protein, and correspond to sequences 39-47 and 333-342. In addition, these CTLs can specifically lyse H-2d target cells transfected with the CS gene. These results suggest that, by immunization of mice with large soluble CS synthetic polypeptides in IFA, it is possible to obtain MHC class I-restricted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vaccines.
Mucosal exudation associated with a pulmonary delayed-type hypersensitivity reaction in the mouse. Role for the tachykinins.
Authors: Buckley T L , Nijkamp F P 
Published: December 2022

Abstract
In this study, the role for sensory neuropeptides in the induction of pulmonary inflammation associated with a delayed-type hypersensitivity (DTH) reaction in the mouse lung was investigated. Dinitrofluorobenzene (DNFB) was used as the sensitizing hapten and dinitrobenzene sulfonic acid was used as the intranasal challenge. Two hours after the challenge, no hapten-specific differences were observed between vehicle- and DNFB-sensitized mice. However, mucosal exudation and leukocyte accumulation (mononuclear leukocytes and neutrophils) were enhanced in the DNFB group 24 h after the challenge. In additional experiments we investigated whether the sensory nerves and specific sensory neuropeptides play a role in this pulmonary DTH reaction. The selective NK1 antagonist (RP 67580; 5.10(-9) mol/mouse), administered 5 min before and 1 h after the challenge, suppressed mucosal exudation and leukocyte accumulation in the airways 24 h after the challenge. In contrast, the selective calcitonin gene-related peptide (CGRP) antagonist, CGRP8-37 (5.10(-9) mol/mouse) had no effect on the pulmonary DTH reaction. Surprisingly, the depletion of all sensory neuropeptides resulted in an enhancement of mucosal exudation in vehicle- and DNFB-sensitized mice 24 h after the challenge. In conclusion, these results demonstrate that the tachykinins are important in mediating mucosal exudation and leukocyte accumulation associated with the DTH reaction in mouse airways. However, the findings in neuropeptide-depleted mice suggest that the sensory nerves may also play a protective role in mouse airways.
Alternatively processed human E-selectin transcripts linked to chronic expression of E-selectin in vivo.
Authors: Chu W , Presky D H , Swerlick R A , Burns D K 
Published: December 2022

Abstract
E-selectin, also known as endothelial leukocyte adhesion molecule-1 (ELAM-1), is transiently expressed on endothelial cells in response to inflammatory cytokines such as IL-1 and TNF-alpha and mediates adhesion of leukocytes. The genomic structure of E-selectin is highly conserved and includes multiple polyadenylation signals and a number of AUUUA transcript destabilizing elements within the 3'-untranslated region (UTR). Anchored-PCR analysis indicates that all three polyadenylation signals within the human E-selectin 3'-UTR are indeed functional, and three forms of E-selectin transcripts (Types I, II, and III) generated by differential usage of these polyadenylation signals were detected in both cytokine-stimulated primary human endothelial cells and human skin tissue cultures. Although the longest transcript (Type III) is the most abundant form found in cytokine-stimulated human endothelial cells and human skin tissue cultures in vitro, only the shortest transcript (Type I) is detected in human dermal biopsies expressing cell surface E-selectin. Interestingly, the Type I E-selectin transcript lacks six of the mRNA destabilizing elements that are thought to mediate rapid degradation of the corresponding mRNA. In agreement with the absence of these mRNA decay signals, we determined that the Type I E-selectin transcript is more stable than the full-length Type III E-selectin transcript in an in vitro chimeric mRNA stability assay. Therefore, the presence of only the Type I transcript in skin biopsies of chronic inflammatory lesions suggests that differential polyadenylation of E-selectin transcripts may provide the molecular basis for the observed chronic expression of E-selectin in human dermal disorders.
Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-beta 1 in promonocytic U-937 cells.
Authors: Lastres P , Almendro N , Bellón T , López-Guerrero J A , Eritja R , Bernabéu C 
Published: December 2022

Abstract
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a widely distributed cell adhesion molecule present on monocytes, macrophages, and monocytic cell lines. Treatment of the promonocytic cell line U-937 with TGF-beta 1 induces homotypic cellular aggregations, simultaneous with an increase in surface expression and specific transcripts of PECAM-1. The TGF-beta-induced cell adhesion phenomena are not dependent on LFA-1, intercellular adhesion molecule-1 (ICAM-1), very late Ag-4 (VLA-4), or very late Ag-5 (VLA-5). However, the phenomena seem to be directly mediated by PECAM-1 because 1) it is inhibited by the addition of Abs or an antisense oligonucleotide specific for PECAM-1; and 2) TGF-beta 1-treated U-937 cells bind to PECAM-1-expressing mouse transfectant fibroblasts, but not to mock transfectants. In addition, this aggregation phenomena are divalent cation-dependent and requires the integrity of the cytoskeleton. Analysis of the intracellular signaling pathways indicates that TGF-beta 1 induces protein kinase C activity, as well as PECAM-1 phosphorylation and association with cytoskeletal components. Furthermore, in this model, an autocrine mechanism for releasing the bioactive form of TGF-beta 1 operates, allowing PECAM-1 activation. These results provide evidence that TGF-beta 1 regulates PECAM-1 function by increasing the expression and activating the adhesion of PECAM-1 in monocytic cells. These two mechanisms seem to be necessary for adhesion because independent inhibition of either expression or activation of PECAM-1 leads to abrogation of cellular aggregation.
Thrombospondin promotes chemotaxis and haptotaxis of human peripheral blood monocytes.
Authors: Mansfield P J , Suchard S J 
Published: December 2022

Abstract
The presence of the extracellular matrix protein thrombospondin (TSP) at sites of tissue injury or inflammation may promote monocyte migration to these sites and play a central role in their eventual differentiation into tissue macrophages. Previously, we have shown that TSP promotes neutrophil adhesion and migration, and primes for oxidant generation. To examine the effect of TSP on monocyte motility, we conducted chemotaxis assays in modified Boyden chambers. TSP was chemotactic for monocytes, with a maximal response at 200 to 500 nM TSP. Checkerboard analysis confirmed that migration was directional. mAb C6.7, against the distal COOH terminus of TSP, inhibited chemotaxis, demonstrating specificity and indicating that the chemotactic activity resides in the COOH terminus. Consistent with the mAb data, the COOH-terminal 140-kDa proteolytic fragment of TSP was chemotactic for monocytes, whereas the NH2-terminal heparin-binding domain was inactive. A synthetic peptide containing the sequence CSVT, derived from the type I repeats of TSP, was also chemotactic. Thus, two different sites on the COOH terminus of TSP are capable of stimulating monocyte chemotaxis. Pertussis toxin, but not cholera toxin, completely inhibited TSP-mediated chemotaxis, suggesting the involvement of GTP-binding proteins. TSP bound to polycarbonate filters stimulated monocyte haptotaxis, with a maximal response at 4 pmol. The directional nature of this motility was confirmed by checkerboard analysis. Monocyte haptotaxis was inhibited by two different mAbs recognizing distinct sites on the COOH terminus. As with chemotaxis, the 140-kDa fragment, but not the heparin-binding domain, contained the haptotactic activity. The CSVT-containing synthetic peptide also promoted monocyte haptotaxis. But, in contrast to chemotaxis, neither pertussis toxin nor cholera toxin inhibited TSP-mediated haptotaxis, suggesting the involvement of a different signal transduction pathway. mAbs against GPIV, beta 1, beta 3, or alpha v integrins did not affect monocyte chemotaxis or haptotaxis, ruling out the involvement of these receptors. These results indicate that TSP is likely to play an important role in monocyte recruitment to an inflammatory or injury site.
IL-12 protects bone marrow from and sensitizes intestinal tract to ionizing radiation.
Authors: Neta R , Stiefel S M , Finkelman F , Herrmann S , Ali N 
Published: December 2022

Abstract
IL-12, a potent stimulator of hemopoietic progenitor cells, was evaluated as a potential protector against 60Co-gamma radiation-induced lethal hemopoietic syndrome in mice. Administration of IL-12 before lethal irradiation of genetically distinct strains of mice, B6D2F1 and C3H/HeJ, protected a significant fraction of both strains of mice from death. Radioprotection was associated with a fivefold increase in the number of bone marrow cells at 6 days after irradiation. Even at supralethal doses of radiation (1200 cGy), the number of c-kit+ bone marrow cells 3 days after irradiation was twofold greater in IL-12-treated mice than in saline-treated mice. However, mice that received IL-12 and 1200 cGy (B6D2F1) or 900 cGy (C3H/HeJ) died of the gastrointestinal syndrome, as was evident by gross necroscopy and histologic evaluation, within 4 to 6 days after irradiation. Induction of the gastrointestinal syndrome in mice not treated with IL-12 required radiation doses of 1500 cGy or greater in both strains. Thus, at doses of radiation at which IL-12 still protects c-kit+ hemopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-stem cell factor Ab. Anti-IFN-gamma Ab did not affect IL-12-induced hemopoietic radioprotection, but abrogated sensitization of the intestinal tract by IL-12. The sensitizing effect of IL-12 may be related to its ability to prime mice to subsequent inflammatory challenge, as demonstrated by an almost 100-fold increase in circulating TNF and IL-6 levels in normal B6D2F1 mice challenged with IL-12 and LPS. This priming effect of IL-12 also was abrogated by anti-IFN-gamma Ab.
Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells.
Authors: Baars P A , Maurice M M , Rep M , Hooibrink B , van Lier R A 
Published: December 2022

Abstract
CD27, a member of the TNFR family, is expressed on most but not all peripheral blood CD4+ T cells. The small fraction of CD4+ T cells with a CD27- phenotype exclusively reside within the CD45RA-CD45RO+ subset. We previously provided evidence that CD27- cells are functionally differentiated cells that have lost CD27 expression as a result of persistent antigenic stimulation. We here show that compared with CD4+CD45RA-CD27+ cells, CD4+CD45RA-CD27- lymphocytes have a high expression of the beta 1 integrins VLA-4 and -5 and of the beta 2 integrin CD11b. Molecules implicated in homing of T cells to peripheral lymphnodes like CD31 and CD62L (L-selectin) are poorly expressed on CD27- cells, whereas receptors involved in organ-specific homing, e.g., cutaneous lymphocyte Ag and HML-1 (alpha E beta 7), are present on CD27- rather than CD27+ T lymphocytes. CD27+ and CD27- cells do not differ notably in the expression of activation molecules such as CD25, CD38, and CD70 (CD27 ligand) but CD7 is markedly absent on approximately half of the CD27- cells. Analysis of mutations in the HPRT gene, as measurement for the amount of cell divisions that have occurred in particular T cell populations in vivo, showed that CD45R0+ cells have a 2 to 5 times higher mutant frequency than CD45RA+ cells, whereas CD45R0+CD27- cells do not differ in this respect from CD45R0+CD27+ cells. In line with this latter finding, cells in G2M phase can only be found in the transitional, CD45RAbrightCD45R0bright subset but not in CD45R0+, CD45RA-, or CD27- cells. Our results imply that the CD27- population contains tissue-specific, specialized "primed" T cells that evolve in vivo independently from extensive cellular division.
Cell cycle control of apoptosis in human leukemic T cells.
Authors: Zhu L , Anasetti C 
Published: December 2022

Abstract
Eukaryotic cell cycle is regulated by feedback controls that can arrest the progress of the cell cycle at specific checkpoints. Failure of feedback controls may predispose cells to undergo apoptotic death in response to a variety of stimuli. Transformed cell lines often carry defects in one or more proteins that regulate cell cycle, and therefore can be used as a model to study how cell cycle controls cell death. The present study investigated whether TCR/CD3-induced apoptosis of human leukemic T cells is cell cycle dependent. Studies of Jurkat and Sup-T13, two human leukemic T cell lines, demonstrated that anti-CD3 Ab-driven activation results in a transient, reversible inhibition of DNA synthesis in Jurkat cells, but results in a persistent, irreversible inhibition of DNA synthesis in Sup-T13 cells. Anti-CD3 mAb blocked Jurkat cells at the G1/S interface without inducing cell death. In contrast, anti-CD3 mAb allowed Sup-T13 cells to enter S phase but inhibited progression into G2 phase and triggered cell death. Electron microscopy showed that anti-CD3 mAb-stimulated Sup-T13 cells acquired the characteristic morphology of apoptosis. The nuclear DNA appeared as oligonucleosome-sized fragments by gel electrophoresis, and as an apoptotic peak displaying lower fluorescence than the DNA content of cells in G1 phase by DNA flow microfluorometry. DNA fragmentation correlated with entry into S phase. The DNA synthesis inhibitor aphidicolin arrested Sup-T13 cells at the G1/S interface and prevented the apoptosis. Therefore, DNA synthesis is required for executing the apoptosis program initiated by TCR/CD3 stimulation of Sup-T13 cells. These data are consistent with the hypothesis that the suicide of activated cycling T cells upon encountering autoantigens may be one of the mechanisms for the immune system to prevent autoimmunity.