bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene.
Authors: Renauld J C , Goethals A , Houssiau F , Merz H , Van Roost E , Van Snick J 
Published: December 2022

Abstract
P40 is a cytokine that was originally identified in the mouse as a T cell growth factor, but whose spectrum of potential targets was recently shown to include mast cells as well as megakaryoblastic leukemic cells. Given these multiple activities, it was proposed that the protein be renamed IL-9. The analysis of P40 genomic clones reported here shows that the human and mouse P40 genes consist of 5 exons spread over approximately 4 kb of DNA and organized in a similar fashion in both species. The two genes exhibit a high degree of identity in the coding sequence and in the 5' untranslated regions, which contain, among other consensus motifs, a conserved sequence for the binding of AP-1. Expression of human P40 was studied in PBMC. Treatment of the cells with PMA and a calcium ionophore induced strong expression of a 0.7-kb P40 mRNA. No message was detected in unstimulated cells or in cells stimulated with LPS or Staphylococcus aureus, indicating that P40 expression is not constitutive and suggesting that the gene is not easily activated in B lymphocytes and in monocytes. By contrast, T cell mitogens such as PHA or anti-CD3 antibodies induced a substantial P40 expression that was further enhanced in the presence of PMA. Cell fractionation experiments indicated that, under these conditions, the protein is preferentially induced in CD4+ T cells. The induction of P40 by anti-CD3 antibodies suggests that P40 production is part of the normal T cell response to antigenic stimulation.
H-2-associated and background genes influence the development of a murine retrovirus-induced immunodeficiency syndrome.
Authors: Makino M , Morse H C , Fredrickson T N , Hartley J W 
Published: December 2022

Abstract
Host genetic determinants of resistance or susceptibility to a retrovirus-induced immunodeficiency syndrome, termed MAIDS, were evaluated in Fv-1b mice infected with the mixture of ecotropic, MCF, and defective murine leukemia viruses designated LP-BM5 murine leukemia viruses. Genes of the MHC were shown to exert a major influence on the development of disease and the extent of virus spread in mice infected as adults. Strains bearing the b, f, k, q, r, and s haplotypes were moderately to highly susceptible to MAIDS whereas mice of the d haplotype were the most resistant. Resistance to disease was strongly associated with inhibition of mink cell focus-inducing virus spread and, to a lesser extent, with inhibition of ecotropic virus expression. Mapping studies localizing resistance associated with the d haplotype to H-2Dd were confirmed by the demonstration that B6 mice carrying this gene as a transgene or by recombination were resistant to disease. Penetrance of resistance to disease associated with expression of H-2Dd was markedly influenced by MHC genes mapping to the left of H-2D and by non-MHC loci such that some strains bearing this gene were highly susceptible to MAIDS. The combined effects of MHC and background genes among 40 strains examined yielded a remarkably wide spectrum of disease phenotypes with the onset of advanced disease ranging from 10 wk to 72 wk postinfection. Resistance to disease in moderately to highly resistant strains was shown to develop with age. Unexpectedly, the disease resistant phenotype was found to be a recessive trait.
Immunoselection of a human melanoma resistant to specific lysis by autologous tumor-infiltrating lymphocytes. Possible mechanisms for immunotherapeutic failures.
Authors: Topalian S L , Kasid A , Rosenberg S A 
Published: December 2022

Abstract
Intratumoral heterogeneity has been proposed as a possible basis for immunotherapeutic failure when tumor-specific agents such as tumor infiltrating lymphocytes (TIL) are employed for cancer therapy. To examine this issue, highly specific oligoclonal MHC class I-restricted cytolytic TIL grown in bulk culture from patient 397 were used to immunoselect a TIL-resistant variant tumor from the autologous cultured melanoma line 397-mel. Four cycles of immunoselection produced tumor 397-R4, a variant completely resistant to 397 TIL but not to allogeneic LAK cell lysis in 4-h 51Cr release assays. By flow microfluorometry analysis, this tumor variant had not lost MHC molecules, adhesion molecules, or a variety of tumor-associated Ag expressed by the parent tumor but showed decreased expression of many Ag examined. Failure of 397-R4 to cold target inhibit TIL lysis of 397-mel suggested that cell-surface modification was at least one mechanism causing TIL resistance. The inherent lysability of 397-R4 was equal to 397-mel, as confirmed by lectin-dependent cellular cytotoxicity, lysis by non-MHC restricted allogeneic TIL, and lysis by a second line of 397 TIL grown independently from tumor 397. Treatment of 397-R4 with IFN-alpha or IFN-gamma, +/- TNF-alpha for 72 h before cytolytic assays enhanced TIL lysis of this target slightly, and enhanced surface expression of MHC class I and II molecules and the adhesion molecule ICAM-1. The resistant phenotype of 397-R4 was evident in all clones of 397-R4 examined and has been maintained in serial culture for over 13 mo and through passage in nude mice, suggesting that such stable tumor variants may provide an in vivo escape mechanism from specific immune reagents such as TIL. Evolving patterns of TIL culture clonality over time, as well as the spontaneous emergence of different clones in two long term TIL cultures grown under identical conditions from the same source of cryopreserved tumor, were documented by analyzing TCR gene rearrangements and suggest that TIL from different culture passages or lines may be used to overcome resistant tumor subpopulations.
Specific prolongation of MHC class II disparate skin allografts by in vivo administration of anti-IFN-gamma monoclonal antibody.
Authors: Rosenberg A S , Finbloom D S , Maniero T G , Van der Meide P H , Singer A 
Published: December 2022

Abstract
In vivo rejection of MHC class II disparate skin allografts has been thought to involve IFN-gamma-induced expression of MHC class II alloantigens because less than 3% of skin epidermal cells express MHC class II alloantigens constitutively. In our study we directly tested this hypothesis by examining the effect of in vivo administered anti-IFN-gamma mAb on rejection of MHC class II disparate skin allografts, and comparing its effect on rejection of MHC class I disparate skin allografts placed on the same individual mice. We found that anti-IFN-gamma mAb blocked the rejection of MHC class II disparate skin allografts, but had no effect on the rejection of MHC class I disparate skin allografts. These results demonstrate that endogenously produced IFN-gamma is critical for rejection of MHC class II disparate skin allografts, but not for rejection of MHC class I disparate skin allografts. Thus, this study strongly supports the concept that MHC class II rejection responses require IFN-gamma induced MHC class II expression on keratinocytes of the allograft.
IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro.
Authors: Guerne P A , Carson D A , Lotz M 
Published: December 2022

Abstract
IL-6 is a regulator of inflammatory and immunological processes and high levels of this cytokine have recently been shown to be present in synovial fluids from inflammatory and degenerative arthropathies. Synovial fluid IL-6 may in part be a product of synoviocytes that have previously been identified as a source of IL-6. To further define intraarticular sources of IL-6, we examined the ability of chondrocytes to produce IL-6 and studied its modulation by inflammatory cytokines and homeostatic regulators of chondrocyte function. Human articular chondrocytes isolated from normal and osteoarthritic joints released low levels of IL-6 when cultured in the presence of serum. The inflammatory cytokines IL-1, and, to a lesser extent, TNF-alpha and IFN-gamma increased IL-6 production. Among the growth factors known to act on chondrocytes, only transforming growth factor-beta, but not epidermal growth factor. fibroblast growth factor, insulin growth factor-1 and 2, platelet growth factor or insulin, was able to significantly increase IL-6 synthesis. Analysis of hormonal influences on chondrocyte IL-6 production showed that testosterone and estradiol synergized with IL-1 in the induction of IL-6. Hydrocortisone, at 10 ng/ml, reduced IL-1-induced IL-6 production by more than 50%. Chondrocyte-derived IL-6 stimulated acute phase protein synthesis and hybridoma cell proliferation. These biological activities were neutralized by a specific antibody to IL-6. Metabolic labeling and immunoprecipitation studies showed that IL-1 induced de novo synthesis of IL-6 and that the IL-6 proteins secreted by chondrocytes were similar to those from fibroblasts. These results demonstrate that chondrocytes are able to produce IL-6 in response to physiologic and inflammatory stimuli. Chondrocytes probably contribute to the increased synovial fluid levels of IL-6 in inflammatory and degenerative conditions of cartilage, and IL-6 may serve as a mediator to coordinate responses to cartilage injury.
MHC regulation in neural cells. Distribution of peripheral and internal beta 2-microglobulin and class I molecules in human neuroblastoma cell lines.
Authors: Lampson L A 
Published: December 2022

Abstract
mAb were used in an immunocytochemical assay to examine beta 2-microglobulin (b2-m) and class I MHC expression in human neuroblastoma cell lines. In lines with weak class I expression among the whole population, under ordinary assay conditions, strong b2-m and class I expression were concentrated in a small subpopulation. In positive cells, Ag was not restricted to any part of the cell body or processes. Strong expression was not required for establishment of any morphologic form or any type of cell contact. These findings complement studies in other experimental systems, where a nonimmunologic role for class I or b2-m in neural cell growth was not revealed. When the microscopic assay was modified to reveal Ag within the internal membrane system, b2-m was detected in every neuroblastoma cell. Most often, the Ag appeared as a ring around the nucleus, or in a punctate distribution in the juxtanuclear area. Internal expression of HLA chains and class I molecules was more difficult to detect, possibly reflecting a normal excess of b2-m. These findings increase understanding of MHC regulation in neural cell lines. They provide the technical and conceptual background for examination of internal MHC Ag in neural tissue.
IL-4 inhibits superoxide production by human mononuclear phagocytes.
Authors: Abramson S L , Gallin J I 
Published: December 2022

Abstract
The activation of mononuclear phagocytes (M phi) and their generation of oxidative products is influenced by various cytokines as well as by normal maturational changes. We examined the effects of IL-4 on superoxide (O2-) production (cytochrome c reduction) by cultured M phi and the modulation of these effects by IFN-gamma and IL-1. Incubation of IL-4 (200 U/ml) with M phi inhibited M phi PMA (100 ng/ml)-stimulated O2-. production by 23% at 24 h, 34% at 48 h, and 70 to 85% at 72 to 96 h. IL-4 similarly inhibited M phi O2-. production in response to zymosan. IL-4 did not affect M phi viability, adherence to microtiter plates, or ability to phagocytose boiled yeast. In comparison with M phi, neutrophil O2-. production was not inhibited after 4 to 20 h incubation with IL-4. When IL-4 was washed out as early as 1 h after the initiation of M phi culture, significant inhibition of O2-. production was observed 4 days later. Sequential addition of either IL-4 or IFN-gamma to cultures demonstrated reciprocal cytokine effects on M phi; IL-4 partially inhibited O2-. production by M phi previously treated with rIFN-gamma whereas rIFN-gamma partially augmented O2-. production by M phi previously treated with IL-4. Because IL-4 has been reported to inhibit IL-1 production, add-back experiments were performed; addition of IL-1 only partly reconstituted O2-. production in IL-4-treated cells. Further characterization showed that although M phi protein synthesis was enhanced by both rIFN-gamma and IL-4 treatment, acid phosphatase, a marker of maturation to the macrophage phenotype, was markedly increased at an earlier time point in IL-4-treated M phi, and correlated with a decline in O2-. production. The ability of IL-4 to suppress M phi O2-. production implicates IL-4 as an important regulator of this aspect of the inflammatory response.
Idiotypic variation in a human B lymphoma cell line.
Authors: Berinstein N , Campbell M J , Lam K , Carswell C , Levy S , Levy R 
Published: December 2022

Abstract
The Ig Id of a B cell lymphoma serves as a distinct marker of the malignant clone and thus as a tumor-specific target for antibody therapy. Somatic variation of the Ig genes expressed by B cell tumors can lead to loss of reactivity with anti-Id antibodies and escape of tumors from the therapeutic effects of such antibodies. In our study, we have used anti-Id antibodies to screen for variants within a cell line derived from a patient with a large cell lymphoma of the B cell type. Cells were simultaneously stained on their surface for idiotypic and for isotypic Ig determinants using reagents labeled with different fluorochromes. Tumor cells expressing intact Ig molecules with alteration of their idiotypic determinants were isolated with the fluorescence activated cell sorter. Idiotypic variation was an ongoing process in vitro with Id- variants being generated at a rate of 2.7 x 10(-4)/cell per generation and Ig- cells being produced at a rate of 1.31 x 10(-5)/cell per generation. Subcloned variants expressed subtle differences in reactivity with a panel of three non-cross-blocking anti-Id antibodies. Analysis of Ig gene rearrangements by the Southern blotting technique using a JH probe established that the variants and the original tumor cells were all clonally related. Immunoprecipitation of surface labeled Ig molecules from the variant subclones disclosed major alterations of the lambda-L chains with no gross alterations of the mu-H chains. Related studies have established that the tumor cells undergo rearrangement and expression of new lambda-L chain genes.
Expression of the V beta 5.1 gene by murine peripheral T cells is controlled by MHC genes and skewed to the CD8+ subset.
Authors: Liao N S , Maltzman J , Raulet D H 
Published: December 2022

Abstract
We have examined the usage of the V beta 5.1 region in peripheral T cell populations of several mouse strains by measuring V beta 5.1 transcript levels. The results show that V beta 5.1 is expressed predominantly by CD8+ T cells in mice of several MHC haplotypes. This finding suggests that V beta 5.1 may confer restriction to class 1 molecules present in these strains. Interestingly, however, T cells expressing V beta 5.1, like those expressing V beta 17a and V beta 11, are clonally deleted from both CD4 and CD8 subsets in mice that express MHC IE molecules. The latter result implies that V beta 5.1 confers reactivity to a class 2 molecule (IE). These results are discussed in terms of positive selection and clonal deletion. Finally we provide evidence that genes in the K or A regions of the MHC also control V beta 5.1 usage.
Ability of human T lymphocytes to adhere to vascular endothelial cells and to augment endothelial permeability to macromolecules is linked to their state of post-thymic maturation.
Authors: Damle N K , Doyle L V 
Published: December 2022

Abstract
The accumulation of mononuclear cells at sites of chronic inflammation is dependent on a number of factors including localized adherence of lymphocytes to vascular endothelial cells (EC), cytokine-mediated increased adhesiveness of endothelium, chemotactic factors and endothelial permeability. The present study investigates two of the above attributes of lymphocyte-EC interaction: namely, the ability of maturationally distinct subpopulations of human T lymphocytes to adhere to vascular EC and to increase vascular endothelial permeability to macromolecules in an in vitro model. Thus, human T lymphocytes were separated into CD4+ CD8-helper/inducer, CD4- CD8+ cytotoxic/suppressor, CD29+ CD45RA- CD45RO+ memory, and CD29- CD45RA+ CD45RO- naive/virgin T subpopulations, were activated with PHA and PMA, and then examined for their adherence to EC and also for their effect on endothelial permeability. Upon activation, cells within each of the above four subpopulations exhibited increased adherence to EC. In contrast, resting CD29+ CD45RA- CD45RO+ memory T lymphocytes exhibited two to three times greater ability to adhere to EC than their CD29- CD45RA+ CD45RO- naive/virgin counterparts. Consistent with their increased adherence to EC, CD29+ CD45RO+ memory T lymphocytes, when activated, significantly increased endothelial permeability to albumin. Although activated CD45RA+ naive T lymphocytes exhibited increased adherence to EC, these cells failed to increase significantly endothelial permeability. Similar to their polyclonal counterparts, Ag-specific CD4+ CD29+ CD45RO+ T cell clones, but not their actively released mediators, also increased endothelial permeability via a noncytolytic mechanism(s). This ability of CD29+ CD45RO+ memory T lymphocytes to augment endothelial permeability may facilitate their transendothelial migration into extravascular space. These observations may provide additional insights into molecular mechanism(s) underlying pathophysiology of localized chronic inflammatory responses in general and more specifically selective accumulation of CD29+/CD45RO+ memory T lymphocytes at sites of chronic inflammation such as rheumatoid synovium.
Phenotypic profile and functions of T cell receptor-gamma delta-bearing cells from patients with primary immunodeficiency syndrome.
Authors: Morio T , Nagasawa M , Nonoyama S , Okawa H , Yata J 
Published: December 2022

Abstract
TCR-gamma delta-bearing T cells have been reported to be increased in several immunodeficient patients. However, their functional role and phenotypic characterization have not yet been well documented. In this study we examined the surface phenotypes and functional properties of TCR-gamma delta+ cells from several patients with primary immunodeficiency syndrome. It was demonstrated that TCR-gamma delta+ cells detected by TCR-delta 1 mAb were increased in some of the patients, particularly in patients with Wiskott-Aldrich syndrome and severe combined immune deficiency. The TCR-gamma delta+ cells showed such a unique profile that more than 60% of the cells expressed delta-TCS1, which is normally present in a lesser amount, and that most of the cells lacked CD5 T lineage marker. TCR-gamma delta+ cells from the patients with primary immunodeficiency syndrome served as NK cells as observed in normal individuals, while displaying weak LAK and allogeneic cell-specific killer activities. The TCR-gamma delta+ cells were classified into several subpopulations according to their antigenic phenotype, then their NK activity of normal individuals and patients, lymphokine-activated killer and allo-specific killer activities of normal individuals were compared among the subpopulations. Delta-TCS1+ cells mediated almost the same killer activities as total TCR-gamma delta+ cells, whereas CD8+ TCR-gamma delta+ cells displayed stronger cytotoxic activities in both normal subjects and the patients with primary immunodeficiency syndrome.
Anti-peptide antibodies detect a lupus-related interspecies idiotype that maps to H chain CDR2.
Authors: Meek K , Takei M , Dang H , Sanz I , Dauphinée M J , Capra J D , Talal N 
Published: December 2022

Abstract
Antibodies to the small nucleoprotein Sm occur spontaneously in human and murine systemic lupus erythematosus. Human and mouse monoclonal anti-Sm autoantibodies designated 4B4 and Y2 share an idiotype (Id) determinant located on the Ig H chain. To understand the molecular basis of this cross-reactivity, the VH regions of both antibodies were sequenced and analyzed for homology. The antibodies showed only 49.6% homology. The second complementary determining region (CDR2) was the most likely candidate for the Id site. To investigate this possibility, rabbit antiserum was made against a peptide corresponding to the CDR2 of 4B4. This antiserum was specific for the immunizing peptide and reacted weakly to a peptide corresponding to the CDR2 of Y2. Anti-CDR2 antibody bound to 4B4 and Y2 but not to other human and mouse mAb. Binding was directed at the H chain when analyzed by Western blots. Anti-CDR2 antibody blocked anti-Id antibody binding to 4B4 and Y2 by 58% and 24%, respectively. These studies suggest that this interspecies Id maps to the H chain CDR2 and that a conserved Id can occur within molecules that are otherwise radically different.
A view of the human idiotypic repertoire. Electron microscopic and immunologic analyses of spontaneous idiotype-anti-idiotype dimers in pooled human IgG.
Authors: Roux K H , Tankersley D L 
Published: December 2022

Abstract
It has previously been reported that up to 40% of the molecules of human IgG from pooled plasma (100,000 donations) spontaneously dimerize, whereas IgG prepared from a single donor contains only trace quantities of dimer. We have conducted immunoelectron microscopic analyses on such samples and have verified that the majority of dimers are composed of complexes in which two arms of each molecule are bound in a reciprocal fashion at or near the distal tips of their respective arms as previously seen in bona fide Id-anti-Id complexes. A significant role for Fc was ruled out by showing the formation of dimeric ring structures in purified F(ab')2 samples. Spontaneous dimerization was also observed in pooled bovine or mouse IgG, but not in that from single animals. Radiolabeled monomeric, single donor human IgG was used as a probe to investigate dimer formation; this material readily codimerized with IgG from other donors or from pooled plasma (either human or bovine), but did not dimerize with IgG from the same donor. Subclass analysis of multiple donor human IgG revealed that the most flexible subclass (IgG3) was overrepresented in the dimer fraction, whereas one of the less flexible subclasses (IgG2) was underrepresented. Although IgG2 could dimerize to some extent with IgG of other subclasses, it could not self-dimerize. These data suggest that structural constraints (hinge flexibility) may play a role in limiting dimerization. This suspicion was confirmed by showing that an additional 15.5% of the monomeric IgG fraction from a multidonor sample could dimerize after a chemically induced increase in hinge flexibility. Our results are interpreted to show that, although the number of functionally distinct Id produced by a species is immense, it is nontheless finite. Moreover, the Id repertoire of an individual is much smaller than that of the species. Pooling the IgG from a number of individuals increases the Id diversity, which increases the chance that any given Id-bearing molecular will encounter a complementary partner.