bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microanatomic clonality of gamma delta T cells in human leishmaniasis lesions.
Authors: Uyemura K , Klotz J , Pirmez C , Ohmen J , Wang X H , Ho C , Hoffman W L , Modlin R L 
Published: December 2022

Abstract
T cells bearing gamma delta Ag receptors accumulate in the lesions of patients with localized American cutaneous leishmaniasis (LCL), and are thought to be involved in immunity to the parasite. To obtain clues as to the nature of the Ag recognized by these cells, we analyzed the diversity of the TCR delta-chain in LCL lesions. Using mAb against variable (V) encoded determinants with immunoperoxidase, both V delta 1 and V delta 2 subpopulations were identified in the dermal granulomas. However, within the epidermis of LCL lesions, the majority of the gamma delta T cells were V delta 1 positive. PCR analysis of lesion-derived DNA using oligonucleotide primers for V and junctional (J) gene segments revealed preferential usage of J delta 1 in lesions compared with the peripheral blood of these patients. Nucleotide sequence analysis of the V-J junction indicated limited diversity of gamma delta T cells within specific microanatomic regions. In addition, use of a single diversity (D) gene segment, D delta 3, in V delta 2 cells in lesions was observed, as opposed to multiple D delta gene segment usage in the blood of the same individuals. The distribution, gene segment usage and clonality of gamma delta T cells in lesions of leishmaniasis was remarkably similar to that observed in leprosy. Therefore, gamma delta T cells responding to infection may recognize a limited set of nominal Ag, perhaps common to distinct pathogens and/or those expressed by the host. Our findings are most consistent with a model in which specific gamma delta T cells are clonally selected by these Ag in lesions and undergo oligoclonal expansion within a microanatomic region.
Differential expression of related HLA class II DQ beta genes caused by nucleotide variation in transcriptional regulatory elements.
Authors: Shewey L M , Beaty J S , Andersen L C , Nepom G T 
Published: December 2022

Abstract
HLA class II genes comprise a large multigene family with intra- and interlocus variation in structure and expression. Within this family of related genes, the HLA-DX alpha and beta loci (HLA DQA2 and DQB2) are highly homologous to functional HLA-DQ loci (HLA DQA1 and DQB1) but are frequently termed pseudogenes because DX gene transcription has not been observed, even in cells expressing HLA-DQ. Analysis of upstream transcriptional regulatory elements for the DX beta and DQ beta genes identified a high degree of nucleotide homology, consistent with their derivation from a common ancestral class II gene. However, transient expression assays with plasmids utilizing promoter elements from the DX beta gene had no activity in transfected human B cells, in contrast to homologous DQ beta sequences. Reciprocal exchange of specific sequences from the DQ beta gene with those of the DX beta gene restored expression to wild-type DQ beta levels, as did mutagenesis of only three DX-specific nucleotides in the upstream regulatory region. These three nucleotides mark two binding sites for distinct nuclear DNA-binding proteins that differentially recognize DQ beta and DX beta sequences. Transcription of these genes is critically dependent on interactions between these two upstream regulatory region sites which distinguish DX beta from its closely related homologue, DQ beta.
The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen.
Authors: Watanabe-Fukunaga R , Brannan C I , Itoh N , Yonehara S , Copeland N G , Jenkins N A , Nagata S 
Published: December 2022

Abstract
The cell surface Fas antigen is a membrane-associated polypeptide which can mediate apoptosis. cDNA clones encoding the Fas antigen were isolated from a cDNA library constructed with mRNA from the mouse macrophage cell line BAM3. The nucleotide sequence and the deduced amino acid sequence of the mouse Fas antigen were 58.5 and 49.3% identical, respectively, to the corresponding sequences of human Fas antigen cDNA. The mouse Fas antigen consists of 306 amino acids with a calculated Mr of 34,971 and contains a single transmembrane domain which divides the molecule into extracellular and cytoplasmic domains. A 2.1-kb mRNA coding for the Fas antigen was detected in the mouse thymus, heart, liver, and ovary but not in brain and spleen. The expression of the Fas antigen gene in mouse fibroblast L929 and macrophage BAM3 cell lines was significantly induced by treatment with IFN-gamma but not by IFN-alpha/beta. Interspecific backcross analysis indicated that the gene coding for the Fas antigen is in the distal region of mouse chromosome 19.
Peptide-presenting similarities among functionally distant HLA-B27 subtypes revealed by alloreactive T lymphocytes of unusual specificity.
Authors: López D , Rojo S , Calvo V , López de Castro J A 
Published: December 2022

Abstract
Functional dissection of HLA-B27 subtypes using alloreactive or B27-restricted CTL has shown that the structurally related B*2704 and B*2706 are the most distant subtypes relative to the prototype B*2705. In particular, previous studies have failed to find anti-B*2705 CTL cross-reacting with B*2704 or B*2706. Such failure can be accounted for by the drastic effect on T cell recognition of the change at residue 152 in both subtypes relative to B*2705, as established with site-directed mutants. B*2704 and B*2706 are also related in ethnic distribution, as they are restricted to Orientals, jointly being the predominant HLA-B27 subtypes in this population. As far as it is known, there are no differences relative to B*2705 in their linkage to ankylosing spondylitis. In our study, 5 of 13 examined anti-B*2705 limiting dilution CTL lines from a particular HLA-B27- individual were shown to crossreact with B*2704, B*2706 or both. The monoclonal nature of this cross-reaction was established by cold target competition analysis. This result demonstrates that the apparent differences in T cell antigenicity among anti-B27 subtypes are strongly influenced by the responder individual, as the spectrum of clonal specificities in anti-B27 responses may show significant differences among unrelated responders. Fine specificity differences among the cross-reactive CTL allowed unambiguous functional distinction between B*2704 and B*2706. The molecular basis of such cross-reactivity was examined by correlating CTL reaction patterns with the structure of both subtypes, which differ only by two residues located in the beta-pleated sheet bottom of the peptide binding site, and with site-directed mutants mimicking HLA-B27 subtype polymorphism. The results suggest that: 1) distinct peptides are involved in the allospecific epitopes recognized by the various crossreactive CTL, and 2) B*2704, B*2706, and B*2705 differ in their peptide-presenting specificity, but can present some identical or structurally similar peptides.
Immunologic disparity in the hypopituitary dwarf mouse.
Authors: Cross R J , Bryson J S , Roszman T L 
Published: December 2022

Abstract
The Snell-Bagg hypopituitary dwarf mouse has been shown to be deficient in growth hormone, thyroxine, and prolactin. There are reports indicating that in addition to these neuroendocrine abnormalities, development of immune competence is also severely impaired in these animals. However, other studies indicate that the immunologic potential of these mice does not differ from their heterozygous littermate controls. Our data show that dwarf mice weaned at 21 days of age and killed at that time, or 7 days later, have reduced numbers of cells in both the spleen and thymus and the mitogen responsiveness of these cells is impaired. However, if mice weaned on day 21 are analyzed at 32 days of age or the mice are weaned at day 30 and analyzed 7 days later the ability to respond to mitogenic stimulation does not differ from controls. Further experiments show that dwarf mice weaned at 30 days of age have a normal complement of V-beta TCR as evidenced by immunofluorescence analysis as well as a primary antibody response to SRBC equivalent to that observed in normal littermates. Immunofluorescence analysis of CD4 and CD8 expression on thymocytes obtained from dwarf mice shows a distinct pattern dependent on the time of weaning and time of analysis. Initial analysis of thymocytes from dwarf mice weaned and killed at 21 days of age do not differ from controls. However, cells from dwarf mice weaned on day 21 and killed on day 28 are markedly different with a loss of immature CD4+/CD8+ cells and a corresponding increase in CD4+ and CD8+ mature thymocytes. In contrast, the phenotype of thymocytes obtained from dwarf mice weaned at 30 days of age and killed on day 37 did not differ from normal littermates. Collectively these studies indicate that hypopituitary dwarf mice lag behind their heterozygous littermates with respect to development of immunocompetence but normal immune responsiveness does develop by 32 days of age when the mice are weaned on day 21.
Diversity in fine specificity and T cell receptor usage of the human CD4+ cytotoxic T cell response specific for the immunodominant myelin basic protein peptide 87-106.
Authors: Martin R , Utz U , Coligan J E , Richert J R , Flerlage M , Robinson E , Stone R , Biddison W E , McFarlin D E , McFarland H F 
Published: December 2022

Abstract
Multiple sclerosis (MS), a human demyelinating disease, is thought to be caused by an autoimmunologic process, and myelin basic protein (MBP) is considered a likely autoantigen. Studies of T cell lines (TCL) responding to different parts of the MBP molecule have indicated that amino acids 87 through 106 contain an immunodominant epitope of MBP. We have demonstrated previously that amino acids 89 through 99 represent the core of this 87-106 peptide epitope. Importantly, this epitope is not only encephalitogenic in SJL/J mice and Lewis rats but also has been shown to be recognized by human cytotoxic TCL in the context of four HLA-DR molecules that are associated with MS in different geographic areas. If the immune response to MBP peptide 87-106 was homogeneous with respect to epitope specificity and TCR usage, specific immunotherapies targeting the interaction of peptide, MHC, and TCR might be possible. In this study, the fine specificity of 29 CD4+ cytotoxic, long term, and limiting dilution TCL that had been generated against whole MBP and were derived from four MS patients and two healthy relatives was dissected using truncated and alanine-substituted peptides for the 87-106 peptide. In addition, the TCR alpha and beta chain usage of 15 CD4+ TCL was determined. Using truncated peptides, the presence of several nested immunogenic epitopes within amino acids 87 to 106 was demonstrated. TCL with identical restriction elements and similar responses to truncated peptides could be differentiated further using alanine-substituted peptides. Finally, heterogeneity of TCR usage was shown not only for those lines that differed in their peptide specificity but also for some that showed identical responses and were restricted by the same HLA-DR antigen. In conclusion, the CD4+ cytotoxic T cell response to the immunodominant MBP peptide 87-106 demonstrates a high degree of heterogeneity at the level of fine specificity and TCR usage. These findings indicate that specific immunotherapies aimed at TCR in MS will probably be more complicated than previously anticipated.
CD4+CD8- thymocytes from neonatal mice induce IgM production in SCID mice.
Authors: Riggs J E , Hobbs M V , Mosier D E 
Published: December 2022

Abstract
Defective recombination of both the TCR and Ig genes results in the absence of mature lymphocytes in mice with the scid mutation. We have shown previously that the transfer of neonatal, but not adult, thymocytes results in high levels of Ig production in 100% of C.B-17-scid (SCID) mice, in contrast to the 10 to 25% of SCID mice spontaneously producing low levels of oligoclonal Ig. In this report we demonstrate that neonatal CD4+8- thymocytes were able to induce this response; the CD4+8+ and CD4-8+ subpopulations were totally inactive and CD4-8- T cells had only limited activity several weeks after transfer. The stimulation of IgM production in SCID mice was detectable by 1 wk posttransfer of CD4+8- thymocytes or splenic T cells, and could be achieved with as few as 300 cells. The ability of neonatal CD4+8- thymocytes to induce Ig diminished gradually to insignificant levels at 3 wk postbirth; this loss of function was not associated with differential survival of neonatal T cells. Neonatal CD4+8- thymocytes from C.B-17 and other H-2d strains rescued Ig production, whereas cells from H-2b, H-2a, and H-2k strains were much less effective. These results suggest that a CD4+8- subpopulation found in both neonatal thymus and peripheral lymphoid tissues is able to induce the expansion or differentiation of the small numbers of functional B lymphocytes in SCID mice, and that the inducing T cell disappears shortly after birth, perhaps during the acquisition of self-tolerance.
Anti-inflammatory action of IL-4. Negative regulation of contact sensitivity to trinitrochlorobenzene.
Authors: Gautam S C , Chikkala N F , Hamilton T A 
Published: December 2022

Abstract
We examined the effects of IL-4, a cytokine produced by Th2 cells, on the development of an Ag-specific, T cell-mediated inflammatory response in a hapten-induced model of contact sensitivity (CS). Intravenous administration of IL-4 was ineffective in modulating the development of CS when administered on days 0, 1, and 2 after sensitization with the hapten trinitrochlorobenzene. In contrast, such treatment significantly reduced the response when given on the day of challenge. Conversely, treatment with anti-IL-4 mAb on day 4 markedly increased the magnitude of CS but was without effect when administered on days 0, 1, and 2. These results suggest that IL-4 interferes with CS at the efferent but not the afferent limb of the response. IL-4 had no inhibitory effect on the ability of immune lymph node cells to transfer adoptively CS or their proliferation upon restimulation with hapten. However, the expression of CS by immune cells was severely curtailed in mice treated with IL-4 prior to immune cell transfer. Furthermore, IL-4 inhibited monokine (gamma-IFN inducible protein [IP-10] and TNF-alpha) expression in macrophages induced by treatment with culture supernatants from the Ag-stimulated immune lymph node cells. These results indicate that suppression of Ag-specific inflammatory CS response by IL-4 may be mediated at least in part through inhibition of cytokine production by mononuclear phagocytes infiltrating the site.
Production of granulocyte-macrophage colony-stimulating factor but not IL-3 by normal and neoplastic human B lymphocytes.
Authors: Zupo S , Perussia B , Baldi L , Corcione A , Dono M , Ferrarini M , Pistoia V 
Published: December 2022

Abstract
The ability of human B cells to produce granulocyte-macrophage (GM)-CSF and IL-3 was investigated. B cells, isolated from tonsils or from the peripheral blood of patients with B cell chronic lymphocytic leukemia using mAb and immune rosettes, were cultured with or without Staphylococcus aureus Cowan strain I. GM-CSF and IL-3 were measured in the culture supernatants using a bioassay based on the selective proliferative response of the MO7e megakaryoblastic cell line to IL-3 or GM-CSF. S. aureus Cowan I-stimulated normal B cells released measurable amounts of GM-CSF but not of IL-3 as determined in neutralization assays with specific mAb in the MO7e cell line test. Some of the unstimulated normal B suspensions also produced GM-CSF, albeit in lower quantities. When normal B cells were fractionated into small (resting) and large (activated) B cells by Percoll density gradients, spontaneous GM-CSF production was detected only in the large cell fractions, but small cells were induced to produce GM-CSF upon S. aureus Cowan I stimulation. On a per cell basis, tonsillar B cells were found capable of releasing more GM-CSF than activated peripheral blood monocytes. The amount of GM-CSF produced by B cells was always inferior to that released by stimulated peripheral blood T cells or NK cells. The purified B cell suspensions from all 14 B cell chronic lymphocytic leukemia patients studied released GM-CSF but not IL-3 in the culture supernatants, sometimes even in the absence of stimuli. Northern blot analysis on total or poly(A)+ RNA confirmed the presence of GM-CSF, but not of IL-3, mRNA transcripts in both normal and malignant B cells. The results of these studies support the notion that activated human B lymphocytes release sufficient GM-CSF to play a role in the control of both hematopoiesis and the inflammatory process.
Immunoregulatory functions of paf-acether. VIII. Inhibition of IL-4-induced human IgE synthesis in vitro.
Authors: Deryckx S , de Waal Malefyt R , Gauchat J F , Vivier E , Thomas Y , de Vries J E 
Published: December 2022

Abstract
In the present study we showed that paf-acether (paf), a naturally occurring phospholipid cytokine, down-regulated IL-4-induced IgE production by mononuclear cells from healthy nonatopic donors in a dose-dependent fashion from 10 microM to 10 pM. Kinetic studies indicated that addition of paf together with IL-4 strongly decreased IgE synthesis from day 7 up to day 14. By contrast, paf had little or no inhibitory effect on the levels of IgM, total IgG, and IgA production. The inhibition of IgE synthesis by paf occurred independently of known inhibitors of IgE synthesis, IFN-gamma, PGE2, and transforming growth factor-beta because the addition of anti-IFN-gamma (10 micrograms/ml) mAb, indomethacin (0.1 microM), or anti-transforming growth factor-beta (10 micrograms/ml) mAb, together with paf and IL-4, did not overcome the inhibition of IgE synthesis. Finally, paf not only inhibited IL-4-induced IgE production but also reduced both germ-line and productive IgE transcripts levels by 77 and 67%, respectively, suggesting that modulation of IgE production by paf occurred at the transcriptional level. Taken together, these results suggest a novel IgE regulatory mechanism by phospholipid cytokine.
Genetic complexity of regulatory mutants defective for HLA class II gene expression.
Authors: Seidl C , Saraiya C , Osterweil Z , Fu Y P , Lee J S 
Published: December 2022

Abstract
MHC (called HLA in man) class II genes play an essential role in cell-mediated immunity. Absence of HLA class II Ag on B lymphocytes is the basis of some congenital immunodeficiencies (CID). We have studied CID by generating transient heterokaryons from cell lines of such patients, and we report that the mutations fall into four complementation groups. In addition, fusions with the HLA class II deletion mutant 721.180 indicate that the genetic defects for each group in HLA class II expression map outside the HLA class II region. A small HLA-DRA promoter fragment is sufficient to drive expression of a reporter gene in normal B cell lines, but expression from the same construct is clearly reduced in mutant cell lines representative of all four complementation groups. This confirms earlier results that indicate defective transcription of HLA class II genes in the class II- CID mutant cell lines. Analysis of proteins that bind to the DRA promoter in nuclear extracts of the mutants suggests that complexes recognizing distinct elements of the DRA promoter may be quantitatively decreased in different mutants. In addition, we show that nuclear extracts from two groups fail to transcribe a DRA promoter construct in vitro accurately reflecting their DRA- phenotypes. In contrast, nuclear extracts from another mutant, RJ2.2.5, transcribe the DRA construct, albeit at a reduced level. Finally, though cell lines from different groups complement each other in vivo, no complementation was observed by mixing extracts for transcription in vitro.
Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions.
Authors: Carlow D A , van Oers N S , Teh S J , Teh H S 
Published: December 2022

Abstract
An in vitro assay was used for assessing the participation of various cell surface molecules and the efficacy of various cell types in the deletion of Ag-specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR specific for the male Ag presented by the H-2Db class I MHC molecule were used as a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR are not subjected to thymic selection as a consequence of the absence of the restricting H-2Db molecule but, nevertheless, express this TCR on the vast majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+ thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro culture with male APC; DC were particularly effective in mediating in vitro deletion when compared with either B cells or T cells. Deletion of CD4+8+ thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA-1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1 beta were without effect. These results are the first direct evidence of LFA-1 involvement in negative selection and provide further direct support for the participation of CD8/class I MHC interactions in this process. Like the requirements for deletion, activation of mature male-specific CD4-8+ T cells from female H-2b TCR-transgenic mice was also largely dependent on Ag presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions; these results support the view that activation and deletion may represent maturation stage-dependent consequences of T cells encountering the same APC. Finally, our results also support the hypothesis that negative selection (deletion) does not require previous positive selection because deletion was observed under conditions where positive selection had not occurred.