bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human epidermal Langerhans cells secrete a soluble receptor for IgG (Fc gamma RII/CD32) that inhibits the binding of immune complexes to Fc gamma R+ cells.
Authors: Astier A , de la Salle H , de la Salle C , Bieber T , Esposito-Farese M E , Freund M , Cazenave J P , Fridman W H , Teillaud J L , Hanau D 
Published: December 2022

Abstract
Langerhans cells (LC) express Fc gamma RII on their cell surface. In this paper, we demonstrate that these cells also release soluble Fc gamma RII (sFc gamma RII) molecules. LC express transcripts encoding a membrane-associated receptor and a transmembrane-deleted Fc gamma RIIA. The latter form was identified in LC culture supernatants using specific antibodies. CHO cells, transfected with LC-derived cDNA encoding the transmembrane-deleted Fc gamma RIIA, secrete sFc gamma RIIA that include the intracellular domain and exhibit the same backbone as the protein identified in LC supernatants. Secreted sFc gamma RIIA exhibits the same pattern of binding to human and mouse IgG subclasses as do membrane Fc gamma RII and inhibits the binding of immune complexes to Fc gamma RII+ cells. In addition, CHO cells expressing the membrane-associated Fc gamma RIIA release truncated and unstable Fc gamma RIIA molecules that lack the intracellular domain. Thus, sFc gamma RII can result from shedding of membrane molecules and/or from secretion of soluble receptors lacking the transmembrane domain.
A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity.
Authors: Larrick J W , Hirata M , Zheng H , Zhong J , Bolin D , Cavaillon J M , Warren H S , Wright S C 
Published: December 2022

Abstract
Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS. Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment. This fragment, designated CAP18(106-142), inhibits many activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS-induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality. CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.
Differential requirement for autoantibody-producing B cells for induction of lymphocytic versus granulomatous experimental autoimmune thyroiditis.
Authors: Braley-Mullen H , Sharp G C , Kyriakos M 
Published: December 2022

Abstract
Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTG transfer experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of anti-IL2R antibody to cultures with MTg leads to activation of cells that induce granulomatous EAT, accompanied by high serum anti-MTg autoantibody responses, in recipient mice. CD4+ T cells are required to induce both forms of EAT; whether B cells and/or autoantibodies produced by MTg-sensitized B cells also contribute to disease severity or the type of thyroid histopathology is unknown. In our study, B cells and autoantibody responses produced in recipient mice were reduced either by column removal of B cells from donor spleen cells or by treatment of recipient mice with anti-I-AK mAb at the time of cell transfer. These maneuvers only slightly reduced the severity of lymphocytic EAT but markedly reduced the severity and incidence of granulomatous EAT developing in recipient mice. Delaying the initiation of anti-I-AK treatment until 6 days after cell transfer was less effective in reducing anti-MTg autoantibody responses or granulomatous EAT. These studies all suggested that anti-MTg autoantibodies were required for development of granulomatous but not lymphocytic EAT. However anti-I-AK-treated recipients receiving injections of anti-MTg antibody or having serum antibody induced by prior immunization with MTg and LPS also developed less severe granulomatous EAT than controls. These results suggest that sensitized CD4+ T cells and circulating anti-MTg autoantibody are not sufficient for development of granulomatous thyroid lesions. It is possible that antibodies having a unique function or specificity are produced in mice developing granulomatous EAT or thyroid-infiltrating B cells may directly contribute to the granulomatous inflammatory response.
Both phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase products are increased by antigen receptor signaling in B cells.
Authors: Gold M R , Aebersold R 
Published: December 2022

Abstract
The effects of Ag binding on B cell development and activation are mediated by intracellular signals initiated by the B cell AgR. In this report, we show that the B cell AgR regulates the production of inositol phospholipids involved in two different signal transduction pathways, the phosphatidylinositol 3-kinase (PtdIns 3-kinase) pathway and the phospholipase C (PLC) pathway. Phosphatidylinositol 3-phosphate (PtdIns3P), phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2], and phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] are produced by PtdIns 3-kinase, an enzyme that appears to be an essential component of tyrosine kinase-mediated signaling. Both PtdIns(3,4)P2 and PtdIns(3,4,5)P3 are likely to function as second messengers in vivo because they can activate the zeta isoform of protein kinase C (PKC) in vitro. We show that cross-linking of the B cell AgR with anti-Ig antibodies caused a five- to sixfold increase in the levels of PtdIns(3,4)P2 in both the mature B cell line BAL 17 and the immature B cell line WEHI-231. PtdIns(3,4)P2 levels increased within 15 s of anti-Ig addition and remained elevated for at least 5 min. AgR cross-linking also caused a slower increase in PtdIns3P levels (approximately 50% over control) and a small, transient increase in PtdIns(3,4,5)P3 levels. Thus, the B cell AgR activates the PtdIns 3-kinase pathway. The other inositol phospholipid signaling pathway involves PLC, which cleaves phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], yielding second messengers that increase intracellular calcium and activate other isoforms of PKC. We analyzed the effects of AgR signaling on PtdIns(4,5)P2 and its precursor, phosphatidylinositol 4-phosphate (PtdIns4P). Consistent with its ability to activate PLC, AgR ligation decreased the levels of PtdIns(4,5)P2. In contrast, AgR cross-linking increased the levels of PtdIns4P. Increased synthesis of PtdIns4P followed by phosphorylation at the D-5 position may prevent depletion of PtdIns(4,5)P2. Thus, signaling by the B cell AgR increases the levels of PtdIns 4-kinase products and PtdIns 3-kinase products. The simplest interpretation of our results is that the B cell AgR activates both PtdIns 3-kinase and PtdIns 4-kinase.
Recovery of T cell populations after acute graft-vs-host reaction.
Authors: Hakim F T , Payne S , Shearer G M 
Published: December 2022

Abstract
We previously have observed that T dependent immune functions were deficient for several months after induction of acute suppressive graft-vs-host-reaction (GVHR) by injection of parental C57BL/10 donor spleen cells into unirradiated (B10 x B10.BR) F, hosts. We therefore investigated whether new T cells matured after acute GVHR, and whether these were tolerant of host Ag. By 8 to 17 mo after GVHR, the frequencies of splenic CD4 and CD8 T cells were found to be comparable to age-matched untreated hosts, although the lymphoid organ size and hence the total number of T cells was significantly reduced. When GVHR was induced with a combination of C57BL/6 (Thy-1.2) mature lymphocytes and B6.PL (Thy-1.1) bone marrow stem cells, the mature donor Thy-1.2 T cells initially predominated during the acute GVHR. After several months, however, 75% of the CD4 and 50% of the CD8 T cell population was derived from donor Thy-1.1% pre-T cells that had matured in the host. Long term GVHR spleen cells were unresponsive to host Ag in CTL assays, but did not suppress anti-host CTL responses. Finally, host-reactive V beta 11 TCR expressing cells were found to be clonally deleted from splenic CD4 and CD8 populations, consistent with intrathymic negative selection. This evidence suggests that the post-GVHR thymus has the capacity to produce and negatively select phenotypically mature CD4 and CD8 T cells and that a failure to clonally delete self-reactive populations is not a contributing factor to the development of chronic GVHR in this system.
B cell IL-7. Human B cell lines constitutively secrete IL-7 and express IL-7 receptors.
Authors: Benjamin D , Sharma V , Knobloch T J , Armitage R J , Dayton M A , Goodwin R G 
Published: December 2022

Abstract
IL-7 was originally reported as a cytokine produced by stromal cells which supports pre-B cell proliferation in vitro. To determine whether human B cells secrete IL-7 and express IL-7R we studied a wide panel of B cell lines (CLS). In Northern blot analysis we detected 2.4 kb IL-7 mRNA and by quantitative PCR we demonstrated IL-7 expression in 5 of 6 B CLS derived from patients with AIDS-associated Burkitt's lymphoma (AABCL), 3 of 3 CLS derived from patients with American Burkitt's lymphoma and 5 of 6 normal lymphoblastoid CLS. Only 1 of 5 African Burkitt's lymphoma CLS and 2 of 7 EBV- CLS expressed IL-7. A total of 484-bp amplicons was cloned and sequenced and found to correspond to the original IL-7 sequence. Constitutive IL-7 secretion was detected in 5 of 6 AABCL and in 6 of 7 normal lymphoblastoid CLS but in none of the 7 EBV- CLS. IL-7R expression was demonstrated in 8 of 26 CLS, none of which secreted IL-7. Our data suggest that 1) IL-7 mRNA is expressed in malignant B cell phenotypes, which correspond to a narrow window in the B cell differentiation pathway (pre-B, early B, intermediate B), as well as in normal lymphoblastoid B CLS. 2) IL-7 mRNA is expressed in both EBV+ and EBV- CLS, but only the EBV+ CLS secrete IL-7. 3) B cells activated by both EBV and HIV-1 (AABCL) secrete the greatest amount of IL-7. 4) IL-7 autocrine loops are not evident since IL-7R were detected on on CLS, which do not secrete IL-7. Our data provide the first direct evidence of IL-7 secretion by human cells and it is yet to be determined whether IL-7 is secreted by other cell types.
Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling.
Authors: Chan A C , van Oers N S , Tran A , Turka L , Law C L , Ryan J C , Clark E A , Weiss A 
Published: December 2022

Abstract
TCR stimulation results in the tyrosine phosphorylation of a number of cellular substrates. We have recently identified a 70-kDa protein tyrosine kinase, ZAP-70, which associates with the human TCR zeta-chain after TCR stimulation. We report here the isolation and sequence of a cDNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93% amino acid identity and are homologous to the 72-kDa protein tyrosine kinase Syk. Syk has been implicated in the signal transduction pathways of the B cell membrane Ig and high affinity IgE receptors, Fc epsilon RI. In addition, we examined the tissue distribution of ZAP-70 and Syk in human and murine thymocyte subsets, B cells, and peripheral T cell subsets. ZAP-70 protein is expressed in all major thymocyte populations, with the level of expression being comparable to that found in both CD4+ and CD8+ peripheral T cells. Although Syk protein is also present in all thymocyte subsets, expression of Syk protein is down-regulated threefold to fourfold in peripheral T cells. In contrast to ZAP-70, expression of Syk is 12- to 15-fold higher in peripheral B cells when compared with peripheral T cells. In addition, whereas T cell stimulation results in down-regulation of Lck, no significant change in ZAP-70 or Syk protein is detected. Finally, we provide evidence that both ZAP-70 and Syk can associate with the TCR after TCR stimulation. With the use of a heterologous expression system, we show that, like ZAP-70, Syk is dependent upon a Src-family protein tyrosine kinase for association with the phosphorylated zeta-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development.
In vitro maturation of human neonatal CD4 T lymphocytes. II. Cytokines present at priming modulate the development of lymphokine production.
Authors: Demeure C E , Wu C Y , Shu U , Schneider P V , Heusser C , Yssel H , Delespesse G 
Published: December 2022

Abstract
The development of naive CD4 T cells into type 1 or type 2 Th cells has been extensively analyzed in the mouse. Using neonatal CD4 T lymphocytes as a source of human naive cells, we report that these cells may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines. After 3 days of stimulation with anti-CD3 mAb immobilized on CD32 transfected mouse fibroblasts, followed by 3 days of culture in the presence of IL-2, neonatal cells acquire the phenotypic and functional characteristics of effector cells. Primed cells are enriched in CD45R0hi and CD31- cells, and upon stimulation with PMA+ ionomycin they release significant amounts of IL-2, IFN-gamma, IL-4, IL-5, and IL-10. Addition of exogenous cytokines during the period of activation with anti-CD3 markedly alters the profile of cytokine production by primed cells: 1) IL-2 uniformly enhances Th1 and Th2 cytokine production; 2) IL-4 markedly enhances the release of IL-4, IL-5, and IL-10 and suppresses that of IFN-gamma; 3) IFN-gamma strongly inhibits IL-4 and IL-5 production but slightly enhances IFN-gamma release; 4) IFN-alpha markedly inhibits IL-4 and IL-5 production and increases the production of both IFN-gamma and of IL-10; 5) TGF-beta suppresses IL-4 and IL-5 (and to a lesser extent IL-2) production but has inconsistent effect on IL-10 and IFN-gamma production. These effects of exogenous cytokines are not associated with an alteration of CD31 expression on primed cells.
TCR V beta 3+ and V beta 6+ CTL recognize tumor-associated antigens related to HER2/neu expression in HLA-A2+ ovarian cancers.
Authors: Peoples G E , Yoshino I , Douville C C , Andrews J V , Goedegebuure P S , Eberlein T J 
Published: December 2022

Abstract
We have recently shown that HLA-A2-restricted, tumor-specific CTL can be isolated from tumor-infiltrating lymphocytes (TIL) in ovarian cancer, and that the sensitivity of ovarian tumors to these CTL is correlated with HER2/neu expression. Furthermore, utilizing PCR, we have documented previously that V beta 2, V beta 3, V beta 6, and V beta 7 are represented in increased proportions in ovarian tumor-specific CTL lines. Therefore, to correlate the interaction of these specific TCR V beta segments with the HLA-A2 molecule and potential tumor-associated Ags (TAA) related to HER2/neu expression, we have utilized available mAbs to V beta 2, V beta 3, and V beta 6. We found that V beta 2+, V beta 3+, and V beta 6+ CTL mediate antitumor activity, and a combination of these mAbs resulted in 83 to 95% inhibition of the cytotoxicity against autologous tumor from three separate patients. These mAbs also were capable of blocking HLA-A2-matched allogeneic cytotoxicity, suggesting that all three V beta families recognize TAA in the context of HLA-A2. An HLA-A2+ melanoma was transfected with the HER2/neu gene and became sensitive to HLA-A2+ ovarian cancer-specific CTL lysis. This cytotoxicity was mediated by V beta 3+ and V beta 6+ CTL, as demonstrated by mAb-blocking studies. FACS-depletion studies confirmed that CTL populations depleted of V beta 3 or V beta 6 no longer could recognize the HER2/neu transfectant. We conclude that V beta 3 and V beta 6 recognize some TAA that are either derived from the HER2/neu protein or induced by the expression of the HER2/neu gene and presented in the context of HLA-A2. Furthermore, V beta 2 seems to recognize an HER2/neu-unrelated Ag system also presented by HLA-A2.
Coronary atherosclerosis in transplanted mouse hearts. II. Importance of humoral immunity.
Authors: Russell P S , Chase C M , Winn H J , Colvin R B 
Published: December 2022

Abstract
Obstructive lesions in arterial vessels of transplanted organs constitute an important factor in the late failure of these organs, especially for the heart. The absence of obstructive lesions in syngeneic donor-recipient combinations, suggests that they depend upon recipient immune responsiveness. It is controversial whether humoral or cellular aspects of the immune response predominate in the process. The present experiments employed hearts transplanted between inbred mice. After brief preoperative immunosuppression of recipients with mAbs to CD4 and CD8 determinants, hearts transplanted between mice incompatible for histocompatibility Ags survived for prolonged periods and most developed typical, obstructive coronary lesions. Our quantitative scoring of vascular changes on tissue sections of excised hearts, grades both their severity and prevalence. Transplants between strains that produced Abs to donor cells (B10.A to B10.BR), developed coronary lesions exceeding those in the reverse combination in which no detectable Ab was formed (B10.BR to B10.A; p &lt; 0.00001), even though their histoincompatibility was similar. Treatment of B10.A recipients of B10.BR hearts with an antiserum against the donor significantly increased coronary lesions (p &lt; 0.0003) in a dose-dependent fashion. Coronary arteries of B10.BR hearts transplanted to C.B-17 SCID mice remained largely free of lesions, whereas transplants to SCID recipients that received continuing injections of an antiserum directed to Ags of the donor developed striking, obstructive coronary lesions. We conclude that humoral immunity can be the prime instigator of atheromatous changes that occur in transplanted hearts.
Identification of CD7 glycoprotein as an accessory molecule in HIV-1-mediated syncytium formation and cellfree infection.
Authors: Sato A I , Balamuth F B , Ugen K E , Williams W V , Weiner D B 
Published: December 2022

Abstract
A major cytopathic effect seen upon in vitro infection of CD4+ human T cells by the HIV is cell-to-cell fusion that results in giant cell (or syncytium) formation. Membrane fusion is required for infection by cellfree virions and in syncytium formation. We report here that the human T cell surface molecule, CD7, is important for the HIV-1 fusion process. CD7 is a roughly 40-kDa glycoprotein member of the Ig supergene family that is expressed early in the ontogeny of thymocytes and on the majority of peripheral blood T cells, as well as on NK cells and a small subpopulation of B cells. Anti-CD7 mAbs inhibited HIV-1-induced cell-cell fusion and prevented cellfree infection of SupT1 cells. The antisyncytial activity of the CD7 Abs is not because of cross-reactivity with CD4 or with viral proteins. Epitope mapping revealed at least two regions of the molecule that are important for preventing membrane fusion. Cells rendered CD7- are poorly infectable by cellfree virus. Additionally, cells rendered CD7- are more easily inhibited from fusing in syncytium formation assays. The collective results support a central role for human CD7 in the process of HIV infection.
Role of CD44 in the development of natural killer cells from precursors in long-term cultures of mouse bone marrow.
Authors: Delfino D V , Patrene K D , DeLeo A B , DeLeo R , Herberman R B , Boggs S S 
Published: December 2022

Abstract
The role of the adhesion molecule CD44 in the development of NK cells was analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture (day 0), recombinant human IL-2 was added and 13 days later the cells generated were shown to have substantial cytotoxic activity against YAC-1 and to be enriched for NK cells, as assessed for NK-1.1 phenotype by flow cytometric analysis. Physical separation between stroma and precursors partially inhibited proliferation and, consequently, a lower number of cytotoxic cells were produced. Similar results were obtained when an anti-CD44 mAb was added together with IL-2 at day 0. The disruption of hyaluronic acid (HA), one of the ligands of CD44, by hyaluronidase or the competition for the binding of CD44 by soluble HA added with IL-2 on day 0 inhibited both proliferation and development of cytotoxicity to a greater degree than did anti-CD44. These results indicate that interaction of CD44 with HA plays an important role in the development of pre-NK cells into cytotoxic effector cells.
Keratinocyte-derived T cell costimulation induces preferential production of IL-2 and IL-4 but not IFN-gamma.
Authors: Goodman R E , Nestle F , Naidu Y M , Green J M , Thompson C B , Nickoloff B J , Turka L A 
Published: December 2022

Abstract
By using superantigens, we have found previously that keratinocytes activated by IFN-gamma could serve as accessory cells, providing costimulatory signals needed to induce T cell proliferation. Here, we compared the profile of cytokines produced by T cells stimulated in the presence of activated keratinocytes with the response seen using professional APCs. When keratinocytes are used as accessory cells there is a specific defect in T cell IFN-gamma production, whereas IL-2 and IL-4 are induced at levels comparable with those seen when professional APCs are used as accessory cells. Because keratinocytes express BB-1, a CD28-ligand distinct from B7-1 or B7-2 (which are found on professional APCs), we examined the possibility that the defect in IFN-gamma production might be a result of nonproductive CD28 engagement. However, even when the CD28 pathway is directly activated by a stimulatory mAb, there is no induction of IFN-gamma production in keratinocyte-supported cultures. In these same cultures IL-2 production is increased 10-fold, thus demonstrating a specific deficiency in the induction of IFN-gamma rather than a failure to respond to CD28 stimulation. Analysis by reverse transcriptase-PCR and ELISA for the inducible p40 chain of IL-12 reveals that keratinocytes produce little if any messenger RNA and no protein for IL-12 p40 compared with professional APCs. Addition of rIL-12 to keratinocyte-supported cultures restores IFN-gamma levels to those seen when professional APCs are present. Finally, when T cells are restimulated and analyzed at later time points (10 to 14 days) we find a refinement in cytokine profiles: T cells stimulated in the presence of professional APCs produced the Th1 cytokines IL-2 and IFN-gamma, whereas T cells stimulated in the presence of activated keratinocytes produced only the Th2 cytokine IL-4. The specific ability of keratinocytes to induce a Th2 response seems most closely linked to their absence of IL-12 production, and may be important in the maintenance of peripheral tolerance to self-Ags or in the immune response to exogenous Ags, pathogens, or haptens encountered in skin.