bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenic and non-mitogenic ligands trigger a calcium-dependent cytosolic acidification in human T lymphocytes.
Authors: Cheung R K , Grinstein S , Gelfand E W 
Published: December 2022

Abstract
We have investigated the patterns of cytosolic pH and Ca2+ ([Ca2+]i) changes after exposure of human peripheral blood T cells to different mitogenic and non-mitogenic ligands. Using ligands that have different accessory cell requirements and varying effect on [Ca2+]i or cell proliferation, we observed that intracellular acidification occurred only with agents that increased [Ca2+]i. However, treatment of the cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, results in significant cytosolic alkalinization without detectable acidification, but did not affect the proliferative responses to mitogenic ligands and was a potent co-mitogen with non-mitogenic ligands. These data indicate that initial acidification or alkalinization responses are not essential for early activation or triggering of DNA synthesis.
Adenosine, deoxyadenosine, and deoxyguanosine induce DNA cleavage in mouse thymocytes.
Authors: Kizaki H , Shimada H , Ohsaka F , Sakurada T 
Published: December 2022

Abstract
When thymocytes were cultured with adenosine, deoxyadenosine, or deoxyguanosine at 1 mM for 24 h, DNA cleavage at internucleosomal sites with multiples of approximately 180 bp was induced, followed by lactate dehydrogenase release into the medium. In the presence of coformycin, an adenosine deaminase inhibitor, or formycin B, a purine nucleoside phosphorylase inhibitor, DNA cleavage was induced by these nucleosides at concentrations of less than 50 microM. Other purine and pyrimidine ribo- and deoxyribonucleosides did not induce DNA cleavage or LDH release. Because thymocyte nuclei contain a Ca2+,Mg2+-dependent endonuclease, which preferentially cuts DNA in its linker regions, DNA fragmentation induced by the three purine nucleosides was suggested to occur through increased activity of the endonuclease. The DNA cleavage induced by the nucleosides required protein phosphorylation and synthesis, inasmuch as it was inhibited by an inhibitor of protein kinases, H-7, and by an inhibitor of protein synthesis, cycloheximide. The inhibition of DNA cleavage was accompanied by a reduction in lactate dehydrogenase release, suggesting a causal relationship between DNA cleavage and cell death. The DNA cleavage and subsequent cell lysis might be related to the selective thymocyte deletion observed in patients with adenosine deaminase or purine nucleoside phosphorylase deficiency.
The response of human marrow colony-forming units-granulocyte and macrophage to inhibition by prostaglandin E and acidic isoferritins is associated with expression of MHC class II antigens and requires the participation of a CD8+ T lymphokine.
Authors: Pelus L M , Levi E , Welte K 
Published: December 2022

Abstract
The in vitro expression of MHC class II Ag by human bone marrow colony-forming unit-granulocyte and macrophage (CFU-GM) and their proliferative response to negative growth regulators in agar culture are transient and can be modulated in vitro by 24-h suspension culture in the presence of PGE. Analysis of the participation of accessory cells in this phenomenon indicates that the ability of PGE to modulate CFU-GM MHC class II expression, the proportion of CFU-GM in S-phase of the cell cycle and the responsiveness of CFU-GM to inhibition in vitro by two negative growth regulators, acidic isoferritin inhibitory activity and PGE itself, requires the participation of CD8+ T lymphocytes. This effect is mediated by a lymphokine of m.w. 27,000 that we have purified to apparent homogeneity. This lymphokine possesses neither colony stimulatory nor inhibitory activity, is produced by both peripheral blood and bone marrow CD8+ T lymphocytes, as well as the CEM T-ALL cell line, and requires the obligatory presence of PGE for activity.
Molecular organization of the DQ subregion (DO-DX-DV-DQ) of the human MHC and its evolutionary implications.
Authors: Blanck G , Strominger J L 
Published: December 2022

Abstract
An overlapping set of cosmid clones from the homozygous DR7 B lymphoblastoid cell line MANN linking the HLA-DO through -DQ subregions is described. This region encompasses 280 kb of DNA, including DQ alpha, DQ beta, DX alpha, DX beta, DO beta, and recently indentified L chain sequences termed DV beta. The orientation and grouping of the alpha- and beta-chains is comparable with an analogous murine class II subregion and also with the HLA-DR alpha and -DR beta chains, suggesting that the arrangement of the constituent genes of class II subregions predates the mouse/human divergence.
Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease.
Authors: Cogné M , Bakhshi A , Korsmeyer S J , Guglielmi P 
Published: December 2022

Abstract
The lack of covalently associated L chains features H chain disease proteins produced in some human B cell lymphoproliferative disorders. We cloned and characterized the single rearranged kappa L chain gene from the leukemic lymphocytes of a patient (RIV) affected with gamma 1 H chain disease, to determine the molecular basis for absent L chain. This kappa allele had undergone an effective V-J rearrangement. Extensive somatic mutation focused about the V-J region created a sequence that was only 75% homologous to its germ-line counterpart. Altered acceptor (V kappa) and donor (J kappa) splice sites resulted in an aberrant splice between the leader and C kappa exons and a truncated 850-bp kappa mRNA. RIV leukemic cells as well as myeloma cells transfected with the RIV kappa gene synthesized a truncated protein. Simultaneous defects in H and L chains genes may reflect a hypermutational mechanism for Ig genes in B cells.
Transcription of T cell antigen receptor genes is induced by protein kinase C activation.
Authors: Lindsten T , June C H , Thompson C B 
Published: December 2022

Abstract
The regulation of expression of the TCR-alpha and -beta genes was studied in the human T cell tumor line Jurkat. Treatment of the cells with PMA was shown to decrease the surface expression of the TCR-alpha/beta/CD3 complex. Subsequent to PMA-induced modulation of the TCR/CD3 complex, increases in the mRNA levels of both the TCR-alpha and -beta genes were observed reaching a maximum 12 h after stimulation. Other T cell activators were also examined for their ability to increase TCR-alpha and -beta mRNA expression. Only agents that activate protein kinase C were shown to induce expression of the TCR-alpha and -beta genes. The observed increases in TCR-alpha and -beta gene mRNA levels were not the result of a uniquely derived Jurkat subline. Similar inductions of TCR-alpha and -beta mRNA levels were observed in an independently maintained Jurkat cell line. In both cell lines, elevations of TCR gene expression was accompanied by a decline in the expression of the c-myc proto-oncogene. PMA induction of TCR-alpha and -beta mRNA was shown to occur in the presence of the protein synthesis inhibitor cycloheximide. The 1.6-kb TCR-alpha and the 1.0-kb D beta J beta C beta TCR-beta gene transcripts were fully induced in the presence of cycloheximide, whereas the 1.3-kb V beta D beta J beta C beta transcript was only partly induced in the presence of cycloheximide. Run-on transcription assays demonstrated that the increase in TCR-alpha and -beta mRNA levels could be entirely accounted for by increases in the transcription rate of both genes after PMA induction. Thus, in summary, protein kinase C stimulation leads to TCR-alpha/beta modulation in Jurkat cells and an increase in steady state TCR-alpha and -beta mRNA levels as a result of transcriptional activation of both genes.
Recognition by cytotoxic T lymphocytes of Qa-2 antigens. Sensitivity of Qa-2 molecules to phosphatidylinositol-specific phospholipase C.
Authors: Mann D , Forman J 
Published: December 2022

Abstract
Con A splenic lymphoblasts were incubated with phosphatidyl-inositol specific phospholipase C (PIPLC) derived from Bacillus thuringiensis and subsequently analyzed for Qa-2 Ag with the Qa-2 reactive mAb Qa-m2. This treatment completely removed Qa-2 detectable Ag on lymphoblasts from H-2d animals, indicating that these molecules are likely anchored to the cell membrane through phosphatidyl inositol (PI). Although exposure of lymphoblasts from H-2b mice to PIPLC greatly reduced Qa-2 expression, a subpopulation of cells retained a limited quantity of the Ag. Bulk cultured anti-Qa-2 CTL generated against the Qa-2 region from H-2b haplotype mice lysed Qa-2+ targets from B6.K2 (H-2b) and BALB/cJ (H-2d) animals. Pretreatment of these lymphoblast targets with PIPLC completely abolished lysis of the BALB/cJ target cells, whereas lysis of B6 targets was reduced only slightly. Anti-Qa-2 CTL clones tested against PIPLC-treated B6 target cells revealed two patterns of reactivity. One group of clones was unaffected in its ability to lyse PIPLC-pretreated targets and cross-reacted on Q6d/Ld molecules expressed on transfected L cells. A second group was unable to lyse PIPLC-pretreated lymphoblasts and cross-reacted on Q7d/Ld targets. These data suggest that H-2b-derived lymphoblasts express two different types of Qa-2 molecules with respect to PIPLC sensitivity; one type is sensitive to PIPLC and cross-reactive with Q7d, the other type is resistant to PIPLC and cross-reactive with Q6d. In contrast, H-2d lymphoblasts express only the PIPLC-sensitive type of molecules. It was also noted that bulk cultured anti-Qa-2 CTL more readily lysed H-2b target cells expressing a smaller quantity of PIPLC-resistant Ag than H-2d targets expressing a larger amount of PIPLC-sensitive Ag. Further, anti-Qa-2 CTL clones readily lysed PIPLC-treated target cells expressing very low levels of serologically detectable Qa-2. This suggests that recognition of class I molecules anchored to the membrane via a PIPLC-resistant linkage may more readily activate CTL for expression of lytic activity than molecules anchored through PI.
Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.
Authors: Cooper S M , Sriram S , Ranges G E 
Published: December 2022

Abstract
Collagen-induced arthritis (CIA) is an experimental model in which a specific immune response to type II collagen (CII) is associated with the development of inflammatory arthritis. In this study, we evaluated the effects of early and delayed treatments with anti-Ia mAb and IFN-gamma on murine CIA. Administration of anti-Ia mAb at the time of immunization with CII decreased the incidence and delayed the onset of arthritis, whereas anti-Ia treatments begun 2 wk after immunization had no effect upon either arthritis incidence or onset. Neither treatment protocol resulted in a significant decrease in antibody titer or proliferative response to CII. Because IFN-gamma increases Ia expression in a variety of cells, we determined its effect on arthritis incidence and onset. When IFN-gamma treatments were begun at the time of immunization the incidence of arthritis was increased and arthritis onset was more rapid. Treatment with IFN-gamma did not result in an increase in anti-CII antibody levels. These results support the importance of Ia expression in the induction of murine collagen-induced arthritis, and suggest that suppression with anti-Ia antibodies and augmentation with IFN-gamma are not the result of changes in the humoral response to CII, but may be due to local effects within the target organ.
Killer cell systems of cynomolgus monkeys experimentally infected with HTLV-1.
Authors: Yoshimura N , Nakamura H , Honjo S , Akiyama N , Hayami M 
Published: December 2022

Abstract
The cell-mediated killer activity in cynomolgus monkeys, which were infected 2.5 yr previously with HTLV-1, was examined. With HTLV-1-infected autologous lymphoid cells as targets, HTLV-1-specific killer cells were not detected among PBL cells of infected monkeys, but in monkeys in which specific memory cells were found. These memory cells were converted to active specific killer cells by stimulation with mytomycin C (MMC)-treated HTLV-1 infected autologous cells in vitro. Target blocking by anti-HTLV-1-related Ag suggested that the target molecules recognized by the specific killer cells may be virus envelope glycoprotein gp 68 and other cellular Ag induced by HTLV-1 infection. In addition to the specific killer cells, NK cells that could kill not only NK-sensitive target cells but also target lymphoid cells with HTLV-1 Ag on their surface, were found in these monkeys. In vitro stimulation caused enhancement of NK cell activity as well as induction of antigen specific killer cells. These findings suggest that Ag-specific killer cells may work together with NK cells to eliminate HTLV-1-bearing T cells in vivo.
Expression of C gamma 4 T cell receptors and lack of isotype exclusion by dendritic epidermal T cell lines.
Authors: Koning F , Yokoyama W M , Maloy W L , Stingl G , McConnell T J , Cohen D I , Shevach E M , Coligan J E 
Published: December 2022

Abstract
Although four murine C gamma gene segments (C gamma 1, 2, 3, and 4) are known to exist, the large majority of expressed gamma-chains have been shown to be of the C gamma 1 isotype and no evidence exists for the expression of more than one receptor by gamma delta TCR-bearing cells. We investigated the nature of the TCR expressed on a number of murine dendritic epidermal T cell-derived cell lines by using both Northern blot and immunoprecipitation analyses. One of these CD3+ cell lines (T195) expresses C gamma 4, V gamma 1, and delta mRNA, and its CD3-associated TCR complex can be precipitated by both anti-C gamma 4 and anti-delta sera, indicating that this receptor is a C gamma 4/delta heterodimer. Furthermore, we show that two cell lines (Y245, Y93) express two distinct TCR gamma-chains, one derived from the C gamma 4 locus, whereas the second gamma-chain is probably derived from the C gamma 2 locus. Together with the previous demonstration of C gamma 1/delta TCR on a number of dendritic epidermal T cell lines (DETC), these results indicate that such DETC are capable of expressing a variety of gamma delta TCR and that, in some DETC, isotype exclusion of gamma-chain expression does not occur.
Macrophage procoagulant-inducing factor. In vivo properties and chemotactic activity for phagocytic cells.
Authors: Ryan J , Geczy C L 
Published: December 2022

Abstract
Murine macrophage procoagulant-inducing factor (MPIF) is a lymphokine with chemical properties distinct from a number of well-characterized cytokines. MPIF induces procoagulant activity on the surface of macrophages and thus may play a central role in the expression of cell-mediated immunity. Highly enriched MPIF-alpha and -beta, separated by virtue of their basic isoelectric point and affinity for heparin, induced local induration and fibrin deposition and cellular infiltration similar to that observed in delayed type hypersensitivity reactions, when injected intradermally. Margination with of polymorphonuclear leukocytes (PMN) along the endothelium as well as increased PMN infiltration was evident after 4 h. In contrast to other inflammatory mediators (e.g., C5a, IL-1) reactivity was sustained, with greater numbers of mononuclear cells apparent 24 h after skin testing. Changes in the dermis were evident 4 h after MPIF injection with increased numbers of cells near areas where spaces in the collagen bundles had formed. Dermal thickening was evident after 24 h and collagen fiber structure was disrupted. Extravascular fibrinogen/fibrin was most prominent 24 h after testing. LPS, which induces macrophage procoagulant activity in vitro, did not induce the histopathologic changes evident with MPIF. MPIF was chemotactic for PMN and macrophages in vitro. Chemotactic activity was heat-labile and not due to C5a. Migration was dependent on a concentration gradient, as determined by checkerboard analysis, indicating that MPIF promoted chemotaxis rather than chemokinesis. Experiments reported here suggest that MPIF is an important mediator of fibrin deposition and cellular infiltration characteristic of cell-mediated immune response.
Cloned cytotoxic T lymphocytes as target cells. II. Polarity of lysis revisited.
Authors: Gorman K , Liu C C , Blakely A , Young J D , Torbett B E , Clark W R 
Published: December 2022

Abstract
The original polarity of lysis experiments suggested that CTL are themselves sensitive to whatever mechanism it is that CTL use to lyse their targets. This concept has placed certain limitations on possible mechanisms of lysis by CTL. Recently, we found in studies with cloned CTL as targets that cloned CTL are in fact highly resistant to lysis by other CTL, as well as to their cytotoxic granule proteins. We show here that although cloned CTL are extremely resistant to lysis by primary and cloned CTL, they are readily inactivated functionally by all primary CTL and by at least one CTL clone. Moreover, cloned CTL are also functionally inactivated by cytotoxic granule proteins. The activation of CTL, which we call inhibitin, is Ca2+ insensitive and distinct from hemolytic activity, and is, thus, unlikely to be perforin. These experiments suggest a possible alternative interpretation of the original polarity of lysis experiments.
Bone marrow cell transplants involving intra-H-2 recombinant inbred mouse strains. Evidence that hemopoietic histocompatibility-1 (Hh-1) genes are distinct from H-2D or H-2L.
Authors: Rembecki R M , Kumar V , David C S , Bennett M 
Published: December 2022

Abstract
Hemopoietic histocompatibility (Hh) Ag are noncodominantly expressed on bone marrow stem cells and other normal and neoplastic cells of hemopoietic origin. H-2/Hh-1 allogeneic or parental-strain bone marrow grafts are eliminated in a determinant specific manner by NK cells. In inbred mouse strains, seven Hh-1 alleles representing combinations of five different Hh-1 antigenic determinants are described. Each Hh-1 allele maps in the vicinity of H-2D, and the genes that map to Hh-1 are transacting regulatory genes. The expression of a particular determinant depends on the absence of the regulatory gene and the presence of the appropriate structural gene. The primary focus of this study is to ascertain whether the Hh-1 phenotype and the serologic H-2DL typing are always correlated or whether recombinant can separate the two. To achieve this, we used a panel of irradiated hosts that are able to recognize the different Hh-1 determinants on the bone marrow cells of congenic intra-H-2 recombinant donors. We report: 1) the majority of strains show a correlation between Hh-1 and H-2DL: 2) B10.RQDB and B10.WB strains dissociate Hh-1 from Lb: 3) nine H-2S/D interval recombinant strains exhibit no correlation between the H-2DL type and Hh-1 phenotype; and 4) in two strains from this group, B10.D2 (R106) and B10.RSF5, H-2S/D crossovers occurred within Hh-1r, (Hh-1 regulatory). We conclude that Hh-1r is a distinct regulatory locus mapping telomeric of H-2S and centromeric of, although probably closer to, H-2D.
Enhancing effect of anti-HLA class I monoclonal antibodies on T cell proliferation induced via CD2 molecule.
Authors: Turco M C , de Felice M , Corbo L , Giarrusso P C , Yang S Y , Ferrone S , Venuta S 
Published: December 2022

Abstract
The mAb 131 to a determinant preferentially expressed on the gene products of the HLA-A locus, the mAb Q6/64 and 4E to determinants preferentially expressed on the gene products of the HLA-B locus, the anti-HLA-A2,A28 mAb CR11-351, HO-2, HO-3, HO-4, and KS1, and the anti-HLA-B7 cross-reacting group mAb KS4 enhanced proliferation of T cells in most, if not all, the PBMC preparations stimulated with the anti-CD2 mAb 9-1 + 9.6. The mAb CR10-215, W6/32, and 6/31 to distinct monomorphic determinants of HLA class I antigens enhanced CD2-induced T cell proliferation in at most 30% of the PBMC preparations tested. The anti human beta 2-microglobulin (beta 2-mu) mAb NAMB-1 displayed no detectable effect on the proliferation of T cells stimulated with the mAb 9-1 + 9.6. The enhancing effect of anti-HLA class I mAb is specific, is dose dependent, is not abrogated by the addition of exogenous IL-1 and IL-2 to the cultures, and reflects the interaction of anti-HLA class I mAb with T cells. Enhancement of CD2 mediated proliferation of T cells is not a unique property of anti-HLA class I mAb, since the anti-HLA class II mAb Q5/6 and Q5/13 also had a similar effect. Analysis of the kinetics of the enhancing effect of anti-HLA class I mAb suggests that they modulate an early event of T cell activation and may affect the interaction of T cells with mAb 9-1. Phenotyping of T lymphocytes activated by mAb 9-1 + 9.6 in the presence of anti-HLA class I mAb suggests that the enhancing effect of anti-HLA class I mAb may reflect the recruitment of a higher percentage of T cells. The present study has shown for the first time that certain, but not all, the determinants of the HLA class I molecular complex are involved in the proliferation of T cells stimulated with the anti-CD2 mAb 9-1 + 9.6. Furthermore, the inhibitory effect of mAb CR11-351, KS1, Q6/64, and W6/32 on the proliferation of T cells stimulated with mAb OKT3 or with mAb BMA 031 indicates that the same determinants of HLA class I antigens play a differential regulatory role in T cell proliferation induced via the CD2 and CD3 pathway.
The alloantibody response in the allogeneically pregnant rat. VI. Detection in maternal serum of specific antigen-antibody complexes.
Authors: Amsden A F , Smith R N , Chirakalwasan N 
Published: December 2022

Abstract
We have examined prepartum and postpartum sera from allogeneically pregnant rats for the presence of paternal antigen using a mAb sandwich assay. Paternal class I antigen, RT1Aa, was frequently detected in postpartum and prepartum rat sera. Postpartum sera from high responders also include anti-RT1Aa alloantibodies, some of which were complexed with the RT1Aa antigen. Although the concentration of antigen is low, the high uterine blood flow causes the amount of class I antigen entering the pregnant female to be in the low microgram per day range. Such an amount could have immunoregulatory significance.
Participation of IL-4 in the formation of IgD-binding factors by antigen-primed mouse spleen cells.
Authors: Adachi M , Arai N , Ishizaka K 
Published: December 2022

Abstract
BALB/c mouse spleen cells primed with either keyhole limpet hemocyanin or DNP-keyhole limpet hemocyanin formed not only IgG-binding factors (BF) and IgE-BF but also IgD-BF upon antigenic stimulation. Analysis of cellular mechanisms involved in the formation of Ig-BF by antigenic stimulation revealed that Ag-primed Th cells released lymphokines upon antigenic stimulation, and that the lymphokine(s) in turn stimulates unprimed T cells to form Ig-BF. Normal unprimed lymphocytes formed IgD-BF upon incubation with culture supernatants of Ag-stimulated spleen cells. The formation of IgD-BF induced by the culture supernatant was prevented by anti-IL-4 mAb (11B11). It was also found that 0.3 to 10 U/ml mouse rIL-4, but none of the rIL-1, IL-2, and IFN-gamma, induced normal T cells to form IgD-BF. Indeed, both IL-2 and IFN-gamma inhibited IL-4 to induce the formation of IgD-BF. In contrast, 10 to 50 U/ml of IFN-gamma induced the formation of IgE-BF, and 50 to 200 U/ml IFN-gamma induced the formation of IgG-BF. However, none of the other lymphokines tested, i.e., IL-1, IL-2, and IL-4, induced the formation of either IgE-BF or IgG-BF. The IgD-BF formed by antigenic stimulation of keyhole limpet hemocyanin-primed spleen cells and those formed by stimulation of normal lymphocytes with 1 to 2 U/ml IL-4 enhanced both IgM and IgG1 plaque-forming cell responses of SRBC-primed spleen cells to homologous Ag. In contrast, 1 to 2 U/ml of IL-4, which could induce the formation of IgD-BF, failed to affect the PFC responses. It appears that the formation of IgD-BF may be involved in the effects of IL-4 to enhance the antibody response.