bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis of immature thymocytes mediated by E2/CD99.
Authors: Bernard G , Breittmayer J P , de Matteis M , Trampont P , Hofman P , Senik A , Bernard A 
Published: December 2022

Abstract
E2/CD99 is a 32-kDa transmembrane molecule that does not belong to any known family of proteins. It appears to regulate adhesion properties of T cells as previously reported, in particular, the induction of homotypic adhesion in CD4+ CD8+ thymocytes. Apoptosis induced via E2/CD99 displays characteristic morphologic features, but includes early mitochondrial alterations and phosphatidylserine exposure at the outer leaflet of the plasma membrane. It is not followed by detectable DNA fragmentation, and its time course is much longer than apoptosis induced via the Fas/CD95 pathway. It requires 18 h for completion. E2/CD99-induced apoptosis does not require any RNA or protein synthesis and still occurs following blockage of the Fas pathway. It is, however, dependent on CPP32 and IL-1beta-converting enzyme-type cysteine proteases, as shown by blockade with their respective specific inhibitors. This effect is restricted to double-positive thymocytes carrying an intermediate density of CD3 and including all CD69+ cells. Thus, E2/CD99 apears to mediate a distinctive apoptotic signal at a critical stage of thymocyte differentiation, i.e., when positive selection is known to occur.
Secretion of soluble pre-B cell receptors by pre-B cells.
Authors: Bornemann K D , Brewer J W , Perez E , Doerre S , Sita R , Corley R B 
Published: December 2022

Abstract
Pre-B cells can express secretory mu (mu(s))- as well as membrane mu (mu(m))-chains. We evaluated the ability of mu(s)-chains to associate with surrogate light chains and assemble into a pre-B cell receptor (BCR) complex in pre-B cells, and explored whether mu(s)-chains could be exploited to generate a secreted soluble pre-BCR. We demonstrate that mu(s)-chains can associate with SLC internally. The mu(s)-containing complexes form higher order polymeric structures, but these are never assembled into completed covalent structures. Instead, the complexes are efficiently retained and rapidly degraded. Alteration of the intracellular redox state by incubation with 2-ME resulted in the secretion of mu(s)-chains, suggesting that they are retained by a thiol-mediated retention mechanism. To identify the sequences on mu(s)-chains responsible for their retention, we generated stable transfectants of a mu-negative pre-B cell line expressing either wild-type or mutant mu(s) constructs. Mutation of a single cysteine (Cys575) in the mu(s) tailpiece resulted in the release and secretion of the mu(s) H chains. These were associated with the surrogate light chain proteins lambda5 and VpreB, and thus appear to constitute an authentic secreted soluble pre-BCR. The soluble pre-BCR has a specificity distinct from Ab consisting of the same heavy chain V region paired with conventional light chains.
Influence of gene-modified (IL-7, IL-4, and B7) tumor cell vaccines on tumor antigen presentation.
Authors: Cayeux S , Richter G , Noffz G , Dörken B , Blankenstein T 
Published: December 2022

Abstract
Tumor cells genetically modified to coexpress certain cytokines (such as IL-7 or IL-4) and B7.1 have increased immunogenicity. Since tumor Ags can be presented either directly by tumor cells or indirectly by host APC (cross-priming), we asked whether B7.1 and IL-7 or IL-4 complemented each other by improving preferentially one or both pathways of Ag presentation. We used TS/A (H-2d) tumor cells and their IL-7, B7, and IL-7/B7 transfectants, and MCA205 (H-2b) tumor cells and their IL-4 and B7 transfectants. beta-galactosidase (beta-gal) was chosen as surrogate tumor Ag. beta-gal has different predominant MHC class I epitopes in H-2d and H-2b mice. Immunization of (H-2b x d)F1 mice with TS/A/beta-gal transfectants showed that both IL-7 and B7.1 and, as control, granulocyte-macrophage CSF augmented cross-priming and rejection of a challenge with MCA205/beta-gal (H-2b). Similarly, immunization with MCA205/beta-gal B7.1 or IL-4 transfectants enhanced cross-priming and rejection of a challenge with TS/A/beta-gal. beta-gal-specific rejection was confirmed by CTL assay. However, direct Ag presentation by tumor cells was enhanced only by B7.1, and not IL-7. For this study, H-2b nu/nu mice reconstituted with F1 lymphocytes were immunized with H-2d TS/A/beta-gal transfectants and challenged with TS/A/beta-gal. In conclusion, indirect Ag presentation was augmented by B7, IL-7, and IL-4, while direct Ag presentation was improved only by B7.
Exogenous CD40 ligand induces a pulmonary inflammation response.
Authors: Wiley J A , Geha R , Harmsen A G 
Published: December 2022

Abstract
Expression of CD40 on cells involved in the inflammatory response has lead to speculation that CD40 ligation could play an important role in the establishment of the inflammatory response. Upon treatment of wild-type CD40 mice with soluble CD40L-CD8 (sCD40L) fusion protein a pulmonary inflammatory response was induced that was not observed in identically treated CD40 knockout mice. This inflammatory response involved polymorphonuclear leukocyte migration into the alveolar space and the accumulation of alveolar macrophages with up-regulated Ia expression. Treatment of wild-type or IFN-gamma knockout mice with sCD40L induced pulmonary responses that were similar except that fewer neutrophils and macrophages accumulated in the lungs of the IFN-gamma knockout mice. This suggested that IFN-gamma plays a role in sCD40L-induced accumulation of inflammatory cells in the lung. The induction of pulmonary inflammation by exogenous sCD40L supports evidence derived in vitro by others that CD40 ligation can result in inflammatory responses and that sCD40L is a potent inflammagen.
The IL-1 system in psoriatic skin: IL-1 antagonist sphere of influence in lesional psoriatic epidermis.
Authors: Debets R , Hegmans J P , Croughs P , Troost R J , Prins J B , Benner R , Prens E P 
Published: December 2022

Abstract
The epidermal expression of IL-1 in psoriasis is clearly altered, but data are still incomplete and poorly understood. To thoroughly study the IL-1 system in psoriasis, we semiquantitatively analyzed the expression of all currently characterized IL-1 isoforms and their receptors in parallel in both lesional (PP) and nonlesional psoriatic (PN) epidermis. Immunostaining of skin sections showed that IL-1alpha, located in the basal keratinocytes of normal control (NN) and PN epidermis, was significantly decreased to negligible levels in PP epidermis. IL-1 receptor antagonist (IL-1ra) and IL-1R type II (IL-1RII) were both significantly overexpressed in mutually exclusive compartments of PP epidermis, the suprabasal and basal compartment, respectively. A significant inverse correlation was found between the expressions of IL-1alpha and these two IL-1 antagonists, which may be inherent to the accelerated terminal differentiation of the psoriatic keratinocyte. In situ hybridization of IL-1(R) mRNAs confirmed the staining results. Levels of IL-1ra mRNA, however, were not increased in PP epidermis, suggesting that the overexpression of IL-1ra protein may be explained at the level of translation. The more sensitive PCR demonstrated a clearly increased expression of IL-1beta mRNA in PP epidermal cells (EC), which may be related to the inflammatory response in psoriasis. IL-1RI mRNA was clearly present in both PP and NN EC. The mRNA levels of the secreted IL-1ra isoform, but not intracellular IL-1raI and II, and IL-1RII were elevated in PP EC and paralleled those of IL-1beta. In summary, this study provides a defined phenotype of the complete epidermal IL-1 system in psoriasis; it shows that the expressions of IL-1(R) isoforms are coordinately altered, resulting in a predominance of IL-1 antagonists, which may represent a negative feedback response to IL-1 agonists, leading to a decreased IL-1 responsiveness.
The integrin-triggered rescue of T lymphocyte apoptosis is blocked in HIV-1-infected individuals.
Authors: Ng T T , Kanner S B , Humphries M J , Wickremasinghe R G , Nye K E , Anderson J , Khoo S H , Morrow W J 
Published: December 2022

Abstract
HIV infection is associated with a disease status-dependent impairment of Ag-specific T cell responses, resulting in anergy or unchecked apoptotic cell death. beta1 integrins play an important role in the induction of T lymphocyte responses to antigenic challenge by providing a T cell costimulatory signal, and have been shown to rescue various cell types from undergoing apoptosis. We examined the integrin-triggered cell survival signal and associated pathways in CD3+ T cells derived from 69 HIV-1-infected individuals in comparison with healthy controls. We found beta1 integrin-mediated costimulation of TCR-induced T cell proliferation and protection from aberrant cell death to be absent in the majority of patients with AIDS, but intact in asymptomatic, infected individuals. The lack of integrin-mediated rescue may be partly due to an early impairment of TCR/integrin-costimulated secretion of IFN-gamma, a type 1 lymphokine that protects against TCR-induced apoptosis of T cells from HIV-seropositive donors, but not loss of integrin expression. The mechanism of integrin hyporesponsiveness appeared to correlate with a failure of the integrin-generated signal to induce pp125FAK mRNA and protein expression. Protein kinase C activation in CD3+ T cells following integrin stimulation was also impaired in HIV-infected individuals, mostly among the symptomatic/AIDS patients. Protein kinase C inactivation in T cells was shown to have a destabilizing effect in vitro on pp125FAK mRNA that contains an AUUUA motif in the 3'-untranslated region, a consensus sequence for the AU-rich elements responsible for mRNA destabilization. These aberrant changes in pp125FAK expression may have direct significance to the overall immunopathogenesis during infection with HIV-1.
Complement Fixation Reaction with Rabies and Herpes Viruses
Authors: Tang Fei-Fang , Castaneda M. Ruiz 
Published: December 2022

Abstract
In 1926 Takaki, Bonis and Koref (1) reported that they had been able to identify and differentiate the various forms of encephalitic viruses by means of the complement fixation reaction. Working on rabies, Kraus and Michalka (2) in the same year published very favorable results in the diagnosis of this disease by complement fixation. They used “cooked” and glycerin extract antigens. Their results were so definite that it was decided to repeat their experiments with rabies, and to use the same technic with herpes, in view of the fact that in herpes studies during the last two years we (3) have carried out a large number of complement fixation experiments with herpes virus, always with negative results.
Technic 1. Immunization of the rabbits Rabbit 1 was immunized against rabies by a prolonged treatment with Semple's vaccine (50 cc. in all) followed by three injections with living fixed virus (3.8 cc. in all).
Cutting Edge: Lyn-Mediated Down-Regulation of B Cell Antigen Receptor Signaling: Inhibition of Protein Kinase C Activation by Lyn in a Kinase-Independent Fashion
Authors: Katsuta Hitoshi , Tsuji Sachiyo , Niho Yoshiyuki , Kurosaki Tomohiro , Kitamura Daisuke 
Published: December 2022

AbstractStimulation of the B cell Ag receptor (BCR) induces activation of tyrosine kinases such as Lyn and Syk, phosphorylation and activation of multiple signaling components, and eventually, the expression of several genes including c-myc. Syk is required for activation of phospholipase C-γ2 and the subsequent phosphatidylinositol hydrolysis, leading to protein kinase C (PKC) activation and intracellular Ca2+ increase. In contrast, the function of Lyn remains obscure. Here, we report that BCR-mediated induction of c-myc promoter activity and of PKC activity, but not the expression level of functional PKC, was markedly augmented in Lyn-deficient chicken B cells. This enhancement was reversed to the level of wild-type cells by the expression of exogenous Lyn of kinase-inactive form. These results indicate that Lyn inhibits BCR-mediated activation of a large portion of PKC isozymes in a kinase-independent fashion. This finding reveals a novel role of Lyn in negative regulation of BCR signaling.
Cross-Linking CD21/CD35 or CD19 Increases Both B7-1 and B7-2 Expression on Murine Splenic B Cells
Authors: Kozono Yuko , Abe Ryo , Kozono Haruo , Kelly Robert G. , Azuma Takachika , Holers V. Michael 
Published: December 2022

AbstractActivation of the complement cascade and ligation of complement C3 receptors on B cells represent an important bridge between innate and Ag-specific acquired immunity. We show here that cross-linking of mouse CD21 (complement receptor type 2, CR2, C3d receptor) and CD35 (complement receptor type 1, CR1, C3b/C4b receptor) or co-cross-linking of CD21/CD35 and surface IgM rapidly up-regulates both B7-1 and B7-2 expression on murine resting splenic B cells. CD21/CD35-mediated up-regulation of both B7-1 and B7-2 expression is observed within 14 h, while other stimuli up-regulate only B7-2 but not B7-1 at this early time point. Consistent with the increase in B7 levels, BALB/c B cells on which surface IgM and CD21/CD35 have been co-cross-linked stimulate C57BL/6 T cells more effectively than controls. This CD21/CD35-enhanced allogeneic MLR is blocked nearly completely by anti-B7-2 mAbs and partially by anti-B7-1 mAbs. In addition, cross-linking of CD19, which is physically associated with CD21/CD35, leads to increased B7-1 and B7-2 expression. These data suggest that CD21/CD35 ligation results in enhanced B cell Ag presentation using costimulatory mechanisms shared with other activators and thus works cooperatively in this process. Rapid up-regulation of B7-1 expression, a unique response to CD21/CD35 and CD19 cross-linking, may be a particularly important effect of C3-containing ligands. We propose that CD21/CD35- and CD19-mediated B7-1 and B7-2 up-regulation is an important mechanism by which complement activation links innate and acquired immunity.
IL-12 Down-Regulates Autoantibody Production in Mercury-Induced Autoimmunity
Authors: Bagenstose Lee M. , Salgame Padmini , Monestier Marc 
Published: December 2022

AbstractIn genetically susceptible H-2s mice, subtoxic doses of mercuric chloride (HgCl2) induce a complex autoimmune syndrome characterized by the production of anti-nucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-induced autoimmunity in H-2s mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in this syndrome. The IL-12 cytokine induces T cell proliferation and IFN-γ production and is necessary for differentiation of naive T cells into the Th1 subset. To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effect of IL-12 administration in mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received HgCl2 plus IL-12, HgCl2 alone, or IL-12 alone. IL-12 treatment resulted in a dramatic reduction of the anti-nucleolar Ab titers. IL-12 also inhibited the HgCl2-induced serum IgG1 increase, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice receiving HgCl2 alone or HgCl2 plus IL-12. Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndrome and that the various manifestations of mercury-induced autoimmunity are independently regulated.
Participation of the CD94 Receptor Complex in Costimulation of Human Natural Killer Cells
Authors: Voss Stephan D. , Daley John , Ritz Jerome , Robertson Michael J. 
Published: December 2022

AbstractOptimal proliferation and expansion of human NK cells require mitogenic cytokines together with cell contact-dependent costimulation. Production of mAb that can modulate human NK cell proliferation yielded NKH3, which recognizes the CD94 Ag. NKH3 immunoprecipitates contain ∼70-kDa heterodimeric complexes consisting of a ∼25-kDa glycoprotein and ∼40- to 45-kDa molecules. Analysis by two-dimensional isoelectric focusing/SDS-PAGE suggests that several different 40- to 45-kDa species are present in the CD94 receptor complex in human NK cells. NKH3 reacted with essentially all resting NK cells, although CD94 is expressed at higher levels on the CD56bright (i.e., high level of CD56) CD16dim/neg (i.e., low level of or absent CD16) subpopulation than on the more abundant CD56dimCD16bright NK cell subset. Moreover, the Z199 mAb, which appears to recognize NKG2-A species that can form heterodimers with CD94, stained virtually all CD56bright NK cells, but only a subset of CD56dim NK cells. Ligation of CD94 augmented the proliferation of CD56bright NK cells in response to IL-2 or IL-15 by as much as 10-fold. Secretion of IFN-γ by CD56bright NK cells stimulated with IL-2 or IL-15 was also enhanced up to 10-fold after CD94 ligation. CD94 mAb did not consistently costimulate proliferation of or IFN-γ production by CD56dim NK cells cultured with IL-2 or IL-15. In contrast, irradiated K562 cells costimulated proliferation of both CD56bright and CD56dim NK cells. These results indicate that CD56bright and CD56dim NK cells can be costimulated through different receptors, which may allow these distinct NK cell subsets to be independently regulated in vivo.
Increased Apoptosis of T Cell Subsets in Aging Humans: Altered Expression of Fas (CD95), Fas Ligand, Bcl-2, and Bax
Authors: Aggarwal Sudeepta , Gupta Sudhir 
Published: December 2022

AbstractAging is associated with lymphopenia and progressive decline in T cell functions; however, the mechanisms underlying these defects are unclear. We analyzed the expression of genes promoting apoptosis (fas/fasL1 and bax) and those inhibiting apoptosis (bcl-2 and bcl-xL) in lymphocytes from aging and young subjects at the protein level, using flow cytometry/Western blotting, and at the mRNA level, using quantitative PCR. Susceptibility of T cell subsets to undergo anti-Fas-induced apoptosis was analyzed by propidium iodide staining, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, DNA fragmentation assay, and staining with Hoechst 33342 dye. An increased expression of Fas and Fas ligand and a decreased expression of Bcl-2 were observed in both CD4+ and CD8+ T cells from aging as compared with young controls. Increased Fas and decreased Bcl-2 expression were also found in memory cells of both CD4+ and CD8+ T cell subsets from aging. Bax expression was increased in lymphocytes from aging at both the protein and mRNA level. No significant difference was observed in Bcl-xL expression between aging and young; however, the ratio of Bax:Bcl-xL was increased in aging. An increased proportion of CD4+ and CD8+ T cell subsets from aging underwent apoptosis following anti-Fas Ab treatment as compared with CD4+ and CD8+ T cell subsets from young controls. These data suggest that increased apoptosis may be one of the mechanisms responsible for lymphopenia and T cell deficiency associated with human aging.
The Cytokine Profile Expressed by Human Dendritic Cells Is Dependent on Cell Subtype and Mode of Activation
Authors: de Saint-Vis Blandine , Fugier-Vivier Isabelle , Massacrier Catherine , Gaillard Claude , Vanbervliet Béatrice , Aït-Yahia Smina , Banchereau Jacques , Liu Yong-Jun , Lebecque Serge , Caux Christophe 
Published: December 2022

AbstractIn the present study, we have analyzed the pattern of cytokines expressed by two independent dendritic cell (DC) subpopulations generated in vitro from human cord blood CD34+ progenitors cultured with granulocyte-macrophage CSF and TNF-α. Molecularly, we confirmed the phenotypic differences discriminating the two subsets: E-cadherin mRNA was only detected in CD1a+-derived DC, whereas CD68 and factor XIIIa mRNAs were observed exclusively in CD14+-derived DC. Semiquantitative reverse-transcriptase PCR analysis revealed that both DC subpopulations spontaneously expressed IL-1α, IL-1β, IL-6, IL-7, IL-12 (p35 and p40), IL-15, IL-18, TNF-α, TGF-β, macrophage CSF, and granulocyte-macrophage CSF, but not IL-2, IL-3, IL-4, IL-5, IL-9, and IFN-γ transcripts. Both subpopulations were shown to secrete IL-12 after CD40 triggering. Interestingly, only the CD14+-derived DC secreted IL-10 after CD40 activation, strengthening the notion that the two DC subpopulations indeed represent two independent pathways of DC development. Furthermore, both DC subpopulations expressed IL-13 mRNA and protein following activation with PMA-ionomycin, but not with CD40 ligand, in contrast to IL-12 and IL-10, revealing the existence of different pathways for DC activation. Finally, we confirmed the expression of IL-7, IL-10, and IL-13 mRNA by CD4+CD11c+CD3− DC isolated ex vivo from tonsillar germinal centers. Thus, CD14+-derived DC expressing IL-10 and factor XIIIa seemed more closely related to germinal center dendritic cellsGCDC than to Langerhans cells.
Dendritic Cells and Resting B Cells Form Clusters In Vitro and In Vivo: T Cell Independence, Partial LFA-1 Dependence, and Regulation by Cross-Linking Surface Molecules
Authors: Kushnir Natalyia , Liu LiMing , MacPherson G. Gordon 
Published: December 2022

AbstractInitiation of an Ab response requires interaction between dendritic cells (DC), T cells, and B cells in a T cell area. We demonstrate that rat DC and B cells form T cell-independent clusters in vitro and in vivo. In vitro clusters form within 1 h and dissociate within 24 to 48 h. Clustering is restricted to resting B cells, is energy, cytoskeleton, and protein kinase C dependent, and is inhibited by anti-LFA-1 but not anti-ICAM-1 mAbs. Spleen and lymph node B cells cluster more strongly than those from lymph or blood, suggesting up-regulation of adhesiveness during transendothelial migration. Bone marrow B cells do not form clusters. DC from spleen and lymph nodes show the most clustering, lymph-borne DC are intermediate, and DC from lamina propria, Peyer’s patches, and those grown from bone marrow form the fewest clusters. Clustering is stimulated by cross-linking MHC class II (whole mAb or F(ab′)2) on DC or B cells or Thy-1 on DC, but not MHC class I, CD45, or CD44. Stimulation by mAb is energy, cytoskeletal, and protein kinase C dependent, but is not inhibited by anti-LFA-1 mAbs, suggesting involvement of other, unidentified adhesion molecules. We suggest that interactions between DC and B cells will occur regularly during B cell recirculation. Cross-linking of MHC class II-peptide molecules on DC by specific T cells would increase binding avidity, causing retention of Ag-specific B cells on DC long enough for the B cells to process Ag, thereby facilitating cognate interactions between T and B cells.