bluuebunny/crossref_metadata_2025_split huggingface dataset:
V beta gene repertoires in aging mice.
Authors: González-Quintial R , Theofilopoulos A N 
Published: December 2022

Abstract
To determine whether aging and thymic involution are associated with defects in intrathymic T cell selection or clonal instabilities, we compared transcript levels for 18 V beta genes in thymic and splenic T cells of young (2 month), adult (12 month), and old (20 month) mice of various Mls and MHC haplotypes (C57BL/6, BALB/c, and DBA/2). The results showed that the unselected thymic V beta repertoires remain stable throughout life, despite severe reduction in cellularity in the thymus of aged mice. Similarly, splenic CD4 and CD8 V beta repertoires showed no significant alterations, and no leakage to the periphery of endogenous superantigen-reactive V beta clones was observed with age, even in irradiated and bone marrow-reconstituted old mice. Responses in vitro to bacterial superantigens were undiminished with age but, significantly, some of these superantigens expanded V beta clones that are cross-reactive with endogenous superantigens and are normally partially (V beta 11 and -12) or severely (V beta 3.1) deleted in BALB/c mice. In the course of these studies, several previously unrecognized reactivities of V beta with staphylococcal toxins were also revealed.
Transcription of unrearranged Ig H chain genes in human B cell malignancies. Biased expression of genes encoded within the first duplication unit of the Ig H chain locus.
Authors: Sideras P , Nilsson L , Islam K B , Quintana I Z , Freihof L , Rosén A , Juliusson G , Hammarström L , Smith C I 
Published: December 2022

Abstract
Analysis of the H chain class switch recombination events on the productive and nonproductive alleles of several human B cell lines has demonstrated that, in the majority of cases, the two loci had rearranged different CH genes. The absence of a strict correlation between the two rearrangement events has been interpreted in favor of a stochastic switching mechanism in human B cells. Based on the accessibility model for the H chain class switch, we have considered an alternative explanation, namely, that transcriptional activation of more than one CH gene could render more than one isotype accessible for recombination. In order to test this possibility, we have stimulated a number of IgM-bearing B cell tumors and analyzed the transcriptional response of their unrearranged C gamma and C alpha H chain genes at the Ig class level by Northern hybridization and at the subclass level by RNA-RNA solution hybridization. Our data show that human clonal B cell populations can simultaneously express germ-line transcripts of both gamma and alpha genes. Our data also demonstrate a bias in the expression of the different isotypes in the B cell chronic lymphocytic leukemias analyzed, with the genes present with the first duplication unit of the H chain locus (gamma 3, gamma 1, and alpha 1) being expressed almost exclusively. These findings indicate that transcriptional activation of large chromosomal regions containing more than one CH gene could render all the genes available for recombination and, therefore, provide an explanation for the asymmetry in the rearrangement events that have previously been described in human B cell tumors. The possible relevance of our findings to the molecular mechanism of the H chain class switch is discussed.
Augmentation of in vivo cytotoxic T lymphocyte activity and reduction of tumor growth by large multivalent immunogen.
Authors: Rogers J , Mescher M F 
Published: December 2022

Abstract
Class I alloantigen incorporated into cell-size supported membranes provides an effective stimulus for in vitro stimulation of CTL responses. When alloantigen-bearing cell-size (5 microns) microspheres, termed large multivalent immunogen (LMI), were administered in vivo, no primary cytotoxic response to the Ag could be detected. However, coadministration of LMI and allogeneic tumor stimulator cells resulted in substantial augmentation of the resulting CTL response, compared with that obtained from mice that received just stimulator cells. Responses were augmented only when the same alloantigen was present on the LMI and on the stimulator cells, and the effector cells remained specific for the cognate alloantigen-bearing targets. The physical form of the alloantigen was critical for augmentation; alloantigen in liposomes had no effect on response levels. Tumor cell Ag in the form of purified plasma membrane vesicles can also be incorporated onto the surface of cell-size microspheres. As with allogeneic responses, tumor Ag on LMI specifically augmented the in vivo CTL activity generated in response to irradiated tumor cells in syngeneic mice. Administration of Ag-bearing LMI to mice inoculated i.p. with live P815, EL4, or RDM4 tumor cells resulted in a significant reduction in growth of the tumors in their syngeneic hosts. Similarly, LMI treatment significantly reduced growth of P815 as a solid s.c. tumor. LMI-mediated growth reduction occurred only when plasma membrane Ag from the cognate tumor was used to prepare the LMI, and Ag in the form of free plasma membrane vesicles was not effective. Although Ag has been used to manipulate in vivo humoral and Th responses, this has proven to be much more difficult for CTL responses. The ability of Ag-bearing LMI to affect significantly the in vivo levels of cytolytic response and to reduce syngeneic tumor growth has potential for application to tumor immunotherapy and, possibly, treatment of other diseases in which CTL can provide a protective effect.
Evidence for clonal expansion of T cell receptor V gamma II+ T cells in the synovial fluid of patients with arthritis.
Authors: Doherty P J , Yang S X , Laxer R M , Silverman E D , Inman R , Pan S 
Published: December 2022

Abstract
We have demonstrated among synovial fluid T cells a unique profile of V gamma II sequences likely arising from clonally expanded T cells. We have determined the junctional diversity associated with each expressed V gamma family by resolving amplified fragments of cDNA into component parts on large denaturing gels. Among synovial fluid T cells we frequently find dominant fragments of a unique size clearly smaller than the dominant band observed with peripheral blood T lymphocytes. In some cases the dominant bands are 12 or 15 nucleotides smaller than the corresponding most abundant band from peripheral blood T lymphocytes. Patterns of lower m.w. species not typical of a polyclonal population argues that clones of T cells expressing the V gamma II family are expanding in the joint and that a high proportion of these cells do not express the V gamma IIJP sequence typical of peripheral blood but rather express V gamma II in combination with a shorter J fragment, JP1, JP2, J1, or J2. In addition by examining joint effusions from the left and right knees from the same individual we have shown that the profiles of V gamma II sequences derived from the fluids are identical to each other but clearly distinct from that of peripheral blood. We have, in addition, quantitated with a series of synthetic internal standards the relative usage of each V gamma family expressed by T cells in the synovial fluid and peripheral blood of seven patients with arthritis including six patients who were either children or adolescents and one adult patient. All patients showed a reduction in the relative expression of V gamma II in synovial T cells relative to peripheral blood T lymphocytes and a corresponding increase in the expression of V gamma I or V gamma III or both. We did not detect expression of V gamma IV in either lymphocyte population.
Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.
Authors: Griffiths M M , Cremer M A , Harper D S , McCall S , Cannon G W 
Published: December 2022

Abstract
Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.
Enhancement of human neutrophil functions by a monoclonal antibody directed against a 19-kDa antigen.
Authors: Mollinedo F , Burgaleta C , Velasco G , Arroyo A G , Acevedo A , Barasoain I 
Published: December 2022

Abstract
A mouse IgG mAb termed P1C3 was raised against A23187-treated human peripheral blood neutrophils and has been shown to recognize an Ag with an apparent molecular mass of 19 kDa, herein named p19. This p19 Ag was weakly expressed at the cell surface of resting human peripheral blood neutrophils and monocytes, but its cell surface expression was dramatically increased upon activation of these cell types with different secretagogues, including FMLP, PMA, and the calcium ionophores A23187 and ionomycin. A large latent pool of p19 molecules became accessible by immunofluorescence flow cytometry after cell permeabilization of resting neutrophils. A practically total translocation of the intracellular pool of this p19 molecule to the plasma membrane was achieved under appropriate cell stimulation, which induced an almost total degranulation of neutrophil secretory granules. The p19 Ag was absent from platelets, PBL, as well as from the human promyelocytic cell line HL-60, the human promonocytic cell line U937, and the human lymphoid cell lines Daudi and Jurkat. The p19 Ag was also expressed by circulating and/or interstitial neutrophils and monocytes in distinct tissues examined. The mAb P1C3 was found to enhance several neutrophil responses, such as chemotaxis, cell adhesion, phagocytosis, and respiratory burst. These data indicate that the mAb P1C3 recognizes an intracellular Ag in human resting mature neutrophils and monocytes, which upon cell activation is translocated to the cell surface and is able to affect cell functionality.
In vitro induction of CD8 expression on thymic pre-T cells. II. Characterization of CD3-CD4-CD8 alpha + cells generated in vitro by culturing CD25+CD3-CD4-CD8- thymocytes with T cell growth factor-beta and tumor necrosis factor-alpha.
Authors: Suda T , Zlotnik A 
Published: December 2022

Abstract
We previously reported that CD25 (IL-2R p55)-positive CD3-CD4-CD8- murine thymocytes can be induced to express CD8 alpha (Lyt-2) by transforming growth factor-beta plus TNF-alpha in the presence of IL-7 (which is necessary to maintain the viability and differentiation capacity of CD25+CD3-CD4-CD8- thymocytes in vitro). The majority of cells recovered after 2 to 3 days from these cultures expressed CD8 alpha (but not CD3 or CD4). In this study, we have characterized these in vitro generated CD3-CD4-CD8 alpha + thymocytes and compared them with normal CD3-CD4-CD8+ thymocytes. Unlike normal CD3-CD4-CD8+ thymocytes that express CD8 alpha and CD8 beta (Lyt-3-chain) simultaneously, only a fraction of in vitro generated CD3-CD4-CD8 alpha + cells expressed CD8 beta. However, along with the induction of CD8 alpha and CD8 beta expression, the expression of other T cell differentiation markers (including CD2, CD25, and CD44) also changed in a manner corresponding to physiologic differentiation. Cell-surface phenotyping suggests that CD8 alpha + beta - cells are less mature than CD8 alpha + beta + cells. These in vitro generated CD3-CD4-CD8 alpha + thymocytes expanded and differentiated into the CD4+CD8+ stage as well as mature (CD3+) single positive (CD4+CD8-) and CD4-CD8+) stages in fetal thymus organ culture that had been depleted of lymphoid cells by treatment with 2-deoxyguanosine. The latter observation indicates that these in vitro generated CD3-CD4-CD8 alpha + thymocytes are responsive to other differentiation-inducing signals (including those that induce CD4) that exist in fetal thymus organ culture. These results suggest that in vitro generated CD3-CD4-CD8 alpha + thymocytes represent intermediate differentiation stages between CD25+CD3-CD4-CD8- and CD3-CD4-CD8+ cells found in normal thymus.
High efficiency presentation of TNP-conjugated islet antigen to islet-specific T cells by a hybrid B cell line expressing TNP-specific surface Ig.
Authors: Wegmann D , Norbury-Glaser M , Bergman B , Haskins K 
Published: December 2022

Abstract
There is compelling evidence from animal models that type I diabetes is a consequence of T cell-mediated destruction of islet beta-cells. The recent isolation of islet-specific T cell clones from nonobese diabetic mice provides a means of identification of the Ag on islet cells that are responsible for stimulation of autoreactive T cells. We describe an APC line constructed by fusion of spleen B cells obtained from nonobese diabetic mice to a B lymphoma that was transfected with the H and L chains of an IgM specific to the hapten TNP. Using this hybrid APC we have observed a dramatic increase in the efficiency of presentation of TNP-conjugated islet cell protein preparations compared to that seen with conventional APC. Our results illustrate the potential use of this APC line for isolation and characterization of islet Ag relevant to the T cell response.
Murine AIDS superantigen reactivity of the T cells bearing V beta 5 T cell antigen receptor.
Authors: Kanagawa O , Nussrallah B A , Wiebenga M E , Murphy K M , Morse H C , Carbone F R 
Published: December 2022

Abstract
A B cell line, B6-1710, that expresses the defective virus known to induce murine AIDS stimulates a large fraction of nonprimed splenic T cells. Analysis of the T cell population responding to the B6-1710 for TCR V beta-chain usage revealed that, in addition to the previously reported V beta 5-chain-positive T cells, T cells bearing V beta 11 and V beta 12 are also specifically enriched. We have established V beta 5+ T cell lines, clones, and hybridomas expressing identical TCR with different CD4/CD8 phenotypes and demonstrated that T cell reactivity to B6-1710 is, although not absolute, dependent on the presence of CD4 molecules. Further analysis of T cell hybridomas with known J beta-chain usage revealed that D beta- and J beta-chain usage do not play crucial roles in T cell reactivity to B6-1710 B cells. However, T cell hybridomas derived from TCR-V beta gene transgenic mice were found to be heterogeneous for their reactivity to B6-1710, suggesting that the V alpha-chains associating with the transgenic V beta-chain determine T cell responsiveness to B6-1710. These data clearly demonstrate that T cell reactivity to a murine AIDS virus expressing B cell line resembles that previously reported for Mls-like superantigens.
Up-regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in murine peritoneal exudate macrophages by both GM-CSF and IL-3.
Authors: Fan K , Ruan Q , Sensenbrenner L , Chen B D 
Published: December 2022

Abstract
Murine peritoneal exudate macrophages (PEM) display multiple CSF receptors. In this study, the expression of granulocyte-macrophage (GM)-CSF receptors in PEM was studied. PEM displayed over 5000 single type, high affinity GM-CSF receptors/cell with a Kd = 38 to 42 pM and an apparent molecular mass of 86,000 Da. Treatment of PEM with low, but not high, concentrations of recombinant murine (rMu) GM-CSF continuously for 24 h resulted in a marked up-regulation of GM-CSF receptors in PEM. A similar up-regulation of GM-CSF receptors also was detected in PEM cultures treated with rMuIL-3 (1-100 ng/ml) for 24 h or longer, regardless the doses of rMuIL-3 added in this case. Scatchard analysis of equilibrium binding showed that the enhanced binding activities in both cases were due to an increase in total number of GM-CSF receptors rather than changes in receptor affinity. Contrariwise, treatment with recombinant human macrophage-CSF (greater than 100-1000 ng/ml) partially inhibited the expression of GM-CSF receptors in PEM. Removal of rMuGM-CSF from culture medium 24 h after treatment led to a further up-regulation of GM-CSF receptors over a 4 to 24-h period, depending on the doses of initial treatment. On the other hand, removal of rMuIL-3 from culture medium after prolonged treatment did not result in further increase in GM-CSF receptors. The protein synthesis inhibitor cycloheximide abrogated GM-CSF receptor up-regulation induced by both rMuIL-3 and rMuGM-CSF, whereas actinomycin D inhibited only the second (8-24 h) phase of GM-CSF receptor up-regulation induced by exposure to high concentrations rMuGM-CSF (10 ng/ml). These findings suggest that rMuGM-CSF and rMuIL-3 up-regulate GM-CSF receptors in PEM in part through similar or identical metabolic pathways and provide further evidence of a close linkage between IL-3 and GM-CSF receptors.
Basement membrane and its components on lymphocyte adhesion, migration, and proliferation.
Authors: Li Y Y , Cheung H T 
Published: December 2022

Abstract
During inflammation and recirculation, lymphocytes migrate into tissues by traversing the capillary endothelium, a process known as extravasation. After crossing the endothelial cells, lymphocytes come into contact with the basement membrane, which is a specialized layer of extracellular matrix containing predominantly laminin, collagen type IV, entactin, and heparan sulfate proteoglycans. In tissue invasion by inflammatory cells and metastatic tumor cells, the basement membrane serves as a substratum for cell adhesion and migration. However, the role of basement membrane in lymphocyte extravasation remains unclear. In this study, we investigated the effect of basement membrane on lymphocyte adhesion, migration, and proliferation, using matrigel as a model for basement membrane. We observed that matrigel promotes both lymphocyte adhesion and migration, with entactin primarily responsible for promoting adhesion and laminin for promoting migration. In addition, activation of lymphocytes by anti-CD3 enhances their adhesion and migration on matrigel-coated substratum. We also observed that matrigel inhibits the proliferation of lymphocytes stimulated by Con A. Furthermore, we demonstrated that laminin is the matrigel component responsible for inhibiting lymphocyte proliferation. However, matrigel has no effect on the proliferation of lymphocytes stimulated by LPS. These results suggest that matrigel has different effects on lymphocyte subpopulations. In agreement with the results on proliferation, matrigel also inhibits the production of IL-2 by Con A-stimulated lymphocytes.
Tumor necrosis factor-alpha-dependent production of reactive nitrogen intermediates mediates IFN-gamma plus IL-2-induced murine macrophage tumoricidal activity.
Authors: Cox G W , Melillo G , Chattopadhyay U , Mullet D , Fertel R H , Varesio L 
Published: December 2022

Abstract
We have previously established that IFN-gamma plus IL-2 induces murine macrophage tumoricidal activity. The purpose of this study was to identify the effector molecules that account for the IFN-gamma plus IL-2-induced macrophage cytotoxicity against P815 mastocytoma cells. ANA-1 macrophages and normal thioglycollate-elicited mouse peritoneal macrophages produced little or no detectable nitrite (NO2-) after incubation with IFN-gamma alone or IL-2 alone; however, IL-2 synergized with IFN-gamma for the production of NO2-. IFN-gamma plus IL-2 did not induce NO2- production or tumoricidal activity in ANA-1 macrophages that were cultured in medium devoid of L-arginine or in ANA-1 macrophages that were incubated with NG-monomethyl-L-arginine. As observed previously with ANA-1 macrophage tumoricidal activity, IL-4 inhibited IFN-gamma plus IL-2-induced, but not IFN-gamma plus LPS-induced, NO2- production. IL-4 also selectively decreased the ability of IFN-gamma and/or IL-2 to augment TNF-alpha mRNA expression in ANA-1 macrophages. Lastly, incubation of ANA-1 macrophages with anti-TNF mAb selectively inhibited the ability of IFN-gamma plus IL-2 to induce NO2- production and tumoricidal activity. These results indicate that IFN-gamma plus IL-2-induced tumoricidal activity is dependent upon the metabolism of L-arginine to reactive nitrogen intermediates, and they establish a role for TNF-alpha as a required intermediate for IL-2-dependent NO2- production and tumoricidal activity.
Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells.
Authors: Quentmeier H , Klaucke J , Mühlradt P F , Drexler H G 
Published: December 2022

Abstract
The mode of IL-6-induced differentiation of Con A-stimulated CD4-CD8+ CTL-P was examined. Through application of neutralizing anti-IL-6, anti-IL-2, and anti-IL-4 mAb it was shown that IL-6 is an "early acting" factor for development of accessory cell-depleted thymocytes. IL-2 and IL-4 are obligatory "late acting" factors for this process. In accordance IL-4, but not IL-6, induced active CTL from CD4-CD8+ CTL-P. The increase of CD4-CD8+ CTL originates at least partially from CD4+CD8+ cells differentiating to active CTL in vitro. CTL development was paralleled by an increase in CD4-CD8+ cells and by a distinct increase in [3H]TdR uptake on day 2 of cultivation. Our data suggest that IL-6 induces Th cells to produce IL-2 and IL-4, the mediators for final differentiation of CD4-CD8+ cells.