bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.
Authors: Iwata S , Hori T , Sato N , Hirota K , Sasada T , Mitsui A , Hirakawa T , Yodoi J 
Published: December 2022

Abstract
Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.
TGF-beta stimulates but IFN-gamma inhibits growth-related activation of locomotion of human B cells.
Authors: Komai-Koma M , Wilkinson P C 
Published: December 2022

Abstract
Effects of TGF-beta and IFN-gamma on locomotion of high density B cells from human tonsils were studied using polarization and filter assays. Culture with TGF-beta (10 pg to 1 ng/ml) induced a gradual increase in locomotor morphologies in 40 to 50% of B cells during overnight culture. This was not immediate (&lt;30 min) suggesting that TGF-beta is not a chemotactic factor. The time course suggests that B cells acquired a locomotor phenotype during the first few hours of culture. B cells cultured in TGF-beta increased in size, but to a lesser extent than those cultured in IL-4 used as a control. More cells were polarized in TGF-beta + IL-4 than in either alone. Following culture in TGF-beta, B cells showed vigorous responses to anti-IgD used as a chemoattractant in short-term assays. In contrast, addition of IFN-gamma (20-100 U/ml) to B cells in culture in IL-4, anti-CD40, or TGF-beta inhibited activation of locomotor capacity by the latter agents, and IFN-gamma-cultured B cells showed an even lower response to anti-IgD in a short-term polarization or filter assay than those cultured in medium alone. IFN-gamma also inhibited uridine incorporation by cultured B cells, and cells cultured in IFN-gamma showed no size increase. We suggest that IFN-gamma prevents locomotor activation by inhibiting progress of B cells into the G1 phase of growth.
T cell development in mice expressing splice variants of the protein tyrosine phosphatase CD45.
Authors: Kozieradzki I , Kündig T , Kishihara K , Ong C J , Chiu D , Wallace V A , Kawai K , Timms E , Ionescu J , Ohashi P , Marth J D , Mak T W , Penninger J M 
Published: December 2022

Abstract
The transmembrane protein tyrosine phosphatase CD45 is expressed in multiple isoforms as a result of alternative splicing of variable exons encoding the extracellular domain. CD45 expression is critical for T cell development, and thymocyte maturation is blocked at the immature CD4+ CD8+ double-positive stage in CD45 gene-deficient (CD45 -/-) mice. Moreover, splicing of variable CD45 exons changes during thymocyte selection. To test the role of CD45 extracellular splice variants in T cell selection and development, we introduced CD45RO (a low-m.w. splice variant lacking exons 4, 5, and 6) and CD45ABC (a high-m.w. isoform containing all exons) transgenes under the control of a thymocyte-specific promoter into a CD45 -/- background, generating CD45RO transgene-positive CD45 -/- (CD45RO) and CD45ABC transgene-positive CD45 -/- (CD45ABC) mice. We demonstrate that both CD45 splice isoforms can rescue development of CD4+ and CD8+ TCR-alphabeta+ thymocytes. Neither CD45 isoform rescued positive selection of H-Y TCR transgene thymocytes, and these cells were blocked at a HSA(high) CD69- CD5(low) stage of development. Peripheral T cells from CD45RO and CD45ABC mice proliferated in response to allogeneic stimulator cells and anti-CD3epsilon cross-linking. However, only CD45RO mice, not CD45ABC mice, generated cytotoxic T cell responses and neutralizing, Th cell-dependent IgG Abs after viral infections. In addition, we show that T cells from CD45RO and CD45ABC mice accumulate in lymph nodes but not in the spleen, liver, or skin, indicating that the CD45 phosphatase may control the homing behavior and trafficking of T cells.
CD16 cross-linking induces both secretory and extracellular signal-regulated kinase (ERK)-dependent cytosolic phospholipase A2 (PLA2) activity in human natural killer cells: involvement of ERK, but not PLA2, in CD16-triggered granule exocytosis.
Authors: Milella M , Gismondi A , Roncaioli P , Bisogno L , Palmieri G , Frati L , Cifone M G , Santoni A 
Published: December 2022

Abstract
The phospholipase A2 (PLA2) enzymes play a central role in diverse cellular processes including phospholipid digestion and metabolism, host defense, and cell signaling. We investigated the ability of CD16 clustering to trigger PLA2 and extracellular signal-regulated kinase (ERK) activation in human NK cells, as well as their possible involvement in CD16-stimulated degranulation. Both secretory (sPLA2) and cytosolic (cPLA2) PLA2 were rapidly activated upon CD16 cross-linking; sPLA2 was found in the supernatant and also in a cell-associated form. cPLA2 activation was controlled by the ERK pathway as indicated by the close correlation between their kinetics of activation and by the ability of the specific MEK inhibitor, PD 098059, to abolish cPLA2 activation. CD16 stimulation also resulted in the generation of platelet-activating factor (PAF) and leukotrienes; both phospholipases contributed to their biosynthesis. Using the pharmacologic inhibitors AACOCF3, p-bromophenacyl bromide (pBPB), and PD 098059, which specifically inhibit cPLA2, sPLA2, and MEK, respectively, we demonstrated that the ERK signaling pathway, but not cytosolic or secretory PLA2, is required for CD16-triggered granule release.
An integrin polymorphism that defines reactivity with alloantibodies generates an anchor for MHC class II peptide binding: a model for unidirectional alloimmune responses.
Authors: Wu S , Maslanka K , Gorski J 
Published: December 2022

Abstract
Polymorphic proteins are often the targets of T and B lymphocytes in alloimmune responses. The polymorphic residue 33 of integrin beta3 is responsible for both a B cell response and a T cell response. Leu at position 33 controls the epitopes recognized by alloantibodies generated in individuals homozygous for Pro at 33. The alloantibody response shows a tight class II MHC restriction, and T cells have been identified that respond to the alloantigen. As part of the T cell response, the alloantigen could be recognized as foreign, and the autoantigen would be ignored due to self-tolerance. Alternatively, the polymorphism could change the ability of the peptide to bind. We tested these two possibilities using synthetic peptides corresponding to the polymorphic region and insect cell-derived class II MHC. The Leu33-containing peptide bound to the restricting MHC allele, whereas the Pro33 peptide did not. Thus, the presence of Leu at position 33 generates an anchor specific for the restricting MHC allele and helps define the peptide binding motif of this allele, HLA-DRB3*0101 (DR52a). These data indicate that certain alloresponses can be viewed entirely as foreign because the polymorphism generates a functional anchor residue in a peptide that otherwise would not bind. On the basis of these results, we would predict a unidirectional alloantibody response as the lack of binding of the Pro33 peptide would preclude T cell help. This could explain the observation that alloantibodies to the Pro33 allele are very rare.
Analysis of the genes encoding the mast cell function-associated antigen and its alternatively spliced transcripts.
Authors: Bocek P , Guthmann M D , Pecht I 
Published: December 2022

Abstract
The mast cell function-associated Ag (MAFA) is a C-type lectin that, upon being clustered, inhibits the Fc epsilon RI stimulation-induced mast cell secretory response. We here report that MAFA is encoded by a single-copy gene that spans 13 kb in the rat genome and is composed of five exons. Three separate exons encode the carbohydrate recognition domain of the MAFA, defining its close homology to the genes of CD23, CD69, CD72, NKR-P1, and Ly49. Functional analysis of the 5' flanking region of the gene reveals that a cell type-specific promoter is located within the first 664 bp upstream of the transcription origin. The promoter lacks any obvious TATA box and drives gene transcription originating from multiple start sites. Examination for possible polymorphism of the MAFA transcripts revealed two novel transcripts, generated by alternative splicing. Deletion of the transmembranal exon in one of them does not result in a frameshift and would, upon translation, give rise to a soluble MAFA molecule. Splicing of two exons in a second transcript results in a new reading frame encoding a putative protein containing MAFA's cytoplasmic domain. The transcription of the MAFA gene was detected in normal rat lungs, where both transmembranal and soluble MAFA appear to be expressed. Lung immunohistochemical analysis further suggests that MAFA expression is restricted to mast cells.
Delivery by Trypanosoma cruzi of proteins into the MHC class I antigen processing and presentation pathway.
Authors: Garg N , Nunes M P , Tarleton R L 
Published: December 2022

Abstract
Class I MHC-restricted T cell responses have been shown to be critical for the development of immune resistance to Trypanosoma cruzi in mice. However, to date, no antigenic targets of this anti-parasite response have been characterized. We have analyzed the characteristics of potential T. cruzi CTL target molecules by expression of the model CTL target molecule chicken OVA in different cellular compartments of T. cruzi. OVA (amino acids 139-385) was expressed as a secretory, cytoplasmic, transmembrane, or glycosylphosphatidylinositol-anchored protein in T. cruzi transfectants. Host cells infected with T. cruzi transfectants that secreted or released OVA, but not those producing cytoplasmic or transmembrane forms of OVA, could process and present OVA peptide via the class I MHC pathway, as indicated by the stimulation of OVA-specific CD8+ T cell hybridomas and the cytolysis of host cells infected with OVA-secreting parasites by OVA-specific CTLs. In addition, infection of mice with OVA-secreting parasites elicited the production of OVA-specific CTLs. These studies demonstrate the ability to target proteins to specific cellular compartments in T. cruzi using either trypanosomal or mammalian signal sequences. Furthermore, these results suggest that proteins secreted or released by T. cruzi in infected cells are a major source of peptides for MHC class I presentation and for the generation of parasite-specific CTL.
IFN-gamma is a prerequisite for optimal antigen processing of viral peptides in vivo.
Authors: Geginat G , Ruppert T , Hengel H , Holtappels R , Koszinowski U H 
Published: December 2022

Abstract
The immediate early protein pp89 of mouse CMV is processed into the nonapeptide YPHFMPTNL, which is presented to CD8+ T lymphocytes by the H-2 Ld molecule. The tissue distribution of this peptide was determined during the course of mouse CMV infection. In tissues, there was no general correlation between peptide processing and infectious virus productivity. Immunosuppression by sublethal irradiation resulted in enhanced MCMV replication but did not increase the peptide yield and drastically reduced the peptide to plaque-forming unit rate in infected organs. IFN-gamma administration restored efficient peptide processing in the immunocompromised host, and neutralization of IFN-gamma in the immunocompetent host decreased peptide processing. This suggests that the efficiency of peptide processing after CMV infection in vivo is governed by IFN-gamma rather than by the productivity of virus infection.
Immunodominant and subdominant CTL responses to Listeria monocytogenes infection.
Authors: Vijh S , Pamer E G 
Published: December 2022

Abstract
Protective immunity to infection by intracellular pathogens begins with expansion of Ag-specific, effector T lymphocytes and is followed by persistence of pathogen-specific memory T cells. Infection by Listeria monocytogenes, an intracellular bacterium, induces cytolytic T lymphocytes that mediate systemic sterilization and long term immunity. In cells infected with L. monocytogenes, H2-Kd class I molecules present three nonamer peptides, listeriolysin (LLO) 91-99, p60 217-225, and p60 449-457, to CTL. Herein we show that during the peak CTL response to L. monocytogenes infection, the ratio of T cells specific for LLO 91-99, p60 217-225, and p60 449-457 is approximately 20:10:1, respectively. While the number of Ag-specific T lymphocytes decreases in the weeks after infection, the proportion of T lymphocytes specific for the three epitopes is maintained. Repertoire analysis of a subset of L. monocytogenes-specific T cells, using alanine-substituted variants of p60 217-225, indicates that the range of T cell specificities is maintained by memory cells. These results indicate that the breadth and relative magnitude of T cell specificities initially elicited by an infection are transmitted to the memory compartment. Our results suggest that T lymphocytes with different gross and fine Ag specificities are equally likely to become memory T cells.
Critical residues on HLA-DRB1*0402 HV3 peptide for HLA-DQ8-restricted immunogenicity: implications for rheumatoid arthritis predisposition.
Authors: Zanelli E , Krco C J , David C S 
Published: December 2022

Abstract
Recently, we have proposed that the combination of HLA-DQ and -DR alleles is responsible for the association of the HLA class II region with rheumatoid arthritis (RA). According to this model, some HLA-DQ alleles, namely DQ4, DQ7, DQ8, and DQ9, predispose carriers to severe RA, but a self peptide of sequence KDILEDERAAVDTYC from the third hypervariable (HV3) region of some DRB1 alleles, including DRB1*0402, can protect from the disease if presented by DQ molecules. This model implies that DQ4, DQ7, DQ8, and DQ9 should be able to present a set of common peptides, despite polymorphisms in their Ag binding groove. In the present study, we have further analyzed the immunogenicity of the DRB1*0402 HV3 peptide in DQ8-transgenic mice. We found that the motif DERAA guarantees DQ8-restricted immunogenicity, and that R is the main anchor residue for binding of the DRB1*0402 peptide to DQ. Interestingly, the p1 pocket that probably controls binding of the R residue is identical in all four RA-associated DQ molecules. Our results imply that the association of RA with some DR subtypes can be explained by their linkage with DQ alleles displaying a binding site for similar "arthritogenic" peptides.
A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation.
Authors: Shin E K , Perryman L E , Meek K 
Published: December 2022

Abstract
The equine SCID defect is more severe than its murine counterpart in that SCID foals are incapable of forming either coding or signal joints, whereas SCID mice manifest normal signal joint formation. To determine the basis of this difference and whether DNA-dependent kinase, catalytic subunit (DNA-PK(CS)), is involved in signal joint formation, equine DNA-PK(CS) transcripts were cloned and sequenced from normal and SCID cell lines. In the mutant allele, a frame-shift mutation truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family resulting in complete absence of full length DNA-PK(CS) and accounting for the kinase-negative phenotype of these cells; the mutation in SCID mice allows for some DNA-PK(CS) expression. The difference in DNA-PK(CS) expression in SCID mice and foals explains the more severe phenotype of equine SCID, and definition of DNA-PK(CS) as the defect in equine SCID demonstrates that DNA-PK(CS) is required for both coding and signal joint formation.
Class I processing-defective Burkitt's lymphoma cells are recognized efficiently by CD4+ EBV-specific CTLs.
Authors: Khanna R , Burrows S R , Thomson S A , Moss D J , Cresswell P , Poulsen L M , Cooper L 
Published: December 2022

Abstract
In the present study, we have isolated CD4+ CTLs that recognize an epitope from EBV nuclear Ag 2 in association with two different HLA-DQ Ags, DQA1*0501/DQB1*0201 (DQ2) or DQA1*0501/DQB1*0301 (DQ7). Both the HLA-DQ2 and HLA-DQ7 alleles displayed a similar efficiency in the endogenous and exogenous presentation of this epitope. Since earlier studies have shown that the EBV-associated malignancy, Burkitt's lymphoma (BL), escapes class I-restricted immune recognition by down-regulating the expression of peptide transporter genes, we have explored the possibility that these tumor cells can process class II-restricted CTL epitopes. The data presented in this study clearly demonstrate that BL cells were recognized efficiently by CD4+, MHC class II-restricted EBV-specific CTLs following infection with recombinant vaccinia encoding EBV nuclear Ag 2. Analysis of surface MHC class II expression on BL cells revealed high levels of HLA-DR and HLA-DQ molecules, and most of these molecules were negative for the invariant chain peptide, referred to as CLIP. Moreover, these tumor cells also showed normal levels of HLA-DMB gene expression, which has been shown previously to be an essential component of the class II processing pathway. The present finding of efficient processing function through the class II pathway in BL cells provides a novel mechanism for immune targeting of EBV-positive malignancies.
CD4+ T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens.
Authors: Khoo U Y , Proctor I E , Macpherson A J 
Published: December 2022

Abstract
T cells from the intestinal mucosal proliferate poorly in vitro, and the contribution of Ag-specific recognition to this hyporesponsiveness is unclear, since the Ag repertoire of intestinal mucosal T cells is unknown. In this study, T cell proliferation in response to Ag-prepulsed autologous peripheral blood-derived APC was examined. Whereas T cells from peripheral blood proliferated to inner membrane and cytoplasmic Escherichia coli proteins, T cells from intestinal mucosa responded only to purified component Ags of these proteins and not to their combination. This suggests that the lack of proliferation in response to these Ags presented as a mixture is not due to the absence of E. coli-specific T cells in the mucosa, but, rather, to down-regulation after T cell recognition. Down-regulation was assayed by measuring the inhibition of autologous peripheral blood T cell proliferation in response to Ag-prepulsed APC. Coculture with leukocytes from intestinal mucosa and not from mesenteric lymph nodes, inhibited autologous peripheral blood T cell proliferation in response to E. coli proteins, but not to tetanus toxoid, PHA, or IL-2. Inhibition was independent of cell contact, provided APC were available to the mucosal cell population, and was reversible by neutralization of IL-10 or TGF-beta with mAb or depletion of mucosal CD4+ T cells. Taken together, the data suggest that mucosal T cell unresponsiveness to luminal Ags is mediated by production of inhibitory cytokines after specific Ag recognition by CD4+ T cells.
Adenosine deaminase binding to human CD26 is inhibited by HIV-1 envelope glycoprotein gp120 and viral particles.
Authors: Valenzuela A , Blanco J , Callebaut C , Jacotot E , Lluis C , Hovanessian A G , Franco R 
Published: December 2022

Abstract
CD26, known to be the adenosine deaminase (ADA)-binding protein, has been implicated in HIV infection. Several studies have revealed a correlation between depletion of CD4+/CD26+ T lymphocytes, increased serum levels of ADA, and the evolution of AIDS in infected individuals. We show that in human B and T cell lines, irrespective of CD4 expression, 125I-labeled ADA binding to CD26 is inhibited by recombinant soluble HIV-1 envelope glycoprotein gp120 and by HIV-1 infectious particles. Accordingly, an anti-CD4 mAb, which inhibits the binding of gp120 to CD4 and blocks viral infection, did not affect inhibition of 125I-labeled ADA binding to CD26 by HIV particles. On the other hand, mAbs directed against the V3 loop and the C-terminal region of gp120 abolished completely the inhibitory effect. Overlapping synthetic peptides covering the entire gp120 sequence were tested to map the region in gp120 responsible for ADA binding inhibition. Only peptides in the C3 region significantly inhibited the binding of ADA to CD26. These results provide indirect evidence for the interaction of gp120 with CD26 and indicate that a specific function of gp120 is the inhibition of ADA binding to CD26 in both CD4+ and CD4- cells. Because ADA deficiency leads to severe combined immunodefiency syndrome, it remains possible that HIV particle-mediated blockade of ADA-CD26 interaction may have significant consequences in the pathogenesis of AIDS.
Human cord blood kappa repertoire.
Authors: Feeney A J , Lugo G , Escuro G 
Published: December 2022

Abstract
To determine the Vkappa gene utilization in cord blood, we made libraries of Igkappa sequences from two cord blood cDNA samples. The rearranged sequences were amplified using random amplification of cDNA ends PCR, ensuring unbiased amplification of all Vkappa genes. Although the human kappa locus contains approximately 38 potentially functional V genes, we observed that approximately 75% of the 146 sequences from our two samples used only nine Vkappa genes. Using leader-specific primers, we also amplified VkappaI and VkappaIII rearrangements from genomic DNA from one of these individuals. Nonproductive rearrangements give an approximation of the relative frequency of gene rearrangement. Some of the genes that were overused in the cDNA libraries were also observed to rearrange frequently, but others did not show high rearrangement frequencies, suggesting that cellular selection caused their increase in the periphery. Surprisingly, we observed a high frequency of rearrangements using L9, which has been reported to be a defective Vkappa gene. Sequence analysis of the unrearranged gene revealed two new functional alleles of this gene. We observed that N nucleotides were present in 29% of the productive sequences from cord blood DNA and RNA. To determine the actual rate of N region addition, we analyzed V-J junctions of rearrangements of two nonfunctional V genes. Forty-six percent of those cord blood sequences contained N regions. In comparison, 57% of junctions of the rearranged nonfunctional gene from adult PBMC contained N regions. Finally, we observed that CDR3 length heterogeneity was more pronounced for VkappaIII genes than for all of the other Vkappa families.