bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ionizing radiation on thymic epithelial cell function. I. Radiation-spared thymic epithelial grafts expedite the recovery of T cell function in lethally irradiated and fetal liver reconstituted mice.
Authors: Wiedmeier S E , Samlowski W E , Rasmussen C J , Huang K , Daynes R A 
Published: December 2022

Abstract
A murine model system was developed to determine whether ionizing radiation has a detrimental influence on thymic epithelium, cell function. Normal mice were lethally irradiated, grafted intracamerally with normal fetal thymic epithelium, and then reconstituted with fetal liver cells. These animals were compared with a group of animals who received their thymic grafts before the irradiation protocol. Analysis of the reconstitution of T cell function in peripheral lymph nodes and spleens at various times post transplantation demonstrated that animals with radiation-spared thymic grafts had superior proliferative responses to T cell mitogens and alloantigens. It was also determined that the capacity of these animals to elicit contact hypersensitivity responses was significantly greater when compared with animals whose thymic grafts had been radiated. The observed difference in T cell function could not be ascribed to a difference in the rate of export of mature T cells from the thymic grafts since the absolute number of Thy-1+, L3T4+, or Lyt-2+ lymphocytes present in the peripheral lymphoid compartment of our two groups of animals was equivalent. Immunohistologic analysis of the thymic grafts demonstrated a marked reduction in the medullary compartment of the repopulated grafts that had been exposed to ionizing radiation. The results of this study suggest: 1) that irradiation of the thymic microenvironment during marrow ablative preparative regimens may be in part responsible for some of the immune alterations observed in marrow transplant recipients, and 2) that our model system may provide a valuable tool for delineating the roles played by medullary and cortical epithelial cells of the thymus on the T cell maturation and education processes.
Inhibition and activation of interleukin 2 synthesis by direct modification of guanosine triphosphate-binding proteins.
Authors: Aussel C , Mary D , Peyron J F , Pelassy C , Ferrua B , Fehlmann M 
Published: December 2022

Abstract
To investigate whether guanosine triphosphate-binding proteins (G proteins) are involved in T cell activation, tests were made of the effect of pertussis toxin, cholera toxin, guanosine 5'-(3-O-thio)-triphosphate, and fluoride ions on interleukin 2 (IL-2) synthesis in Jurkat cells. It was found: 1) that pertussis toxin interferes with the first pathway of T cell activation insofar as it can substitute for phytohemagglutinin or monoclonal antibodies directed against the CD3 surface proteins, suggesting that a G protein serves as transducer for signals via the T cell receptor-CD3 complex; and 2) that fluoride ions induce the release of diacylglycerol (DAG) from [3H] arachidonic acid or [3H]oleic acid-prelabeled cells. In [3H]inositol or 32P-prelabeled cells, the increase in DAG production was also found to be accompanied by a 280% increase of intracellular inositol phosphate (IP), without significant modification of IP2 and IP3. These results suggest that a G protein controls the activity of a phospholipase C in Jurkat cells that upon stimulation releases DAG but not IP3. Inasmuch as DAG, like the phorbol ester tetradecanoyl phorbol acetate, activates protein kinase C, it suggests that a G protein is also involved in the transduction of the second signal for lymphocyte activation. Fluoride ions were found to be as effective as tetradecanoyl phorbol acetate to stimulate IL-2 synthesis in Jurkat cells when used in combination with phytohemagglutinin. Finally, cholera toxin and guanosine 5'-(3-O-thio)-triphosphate were found to increase intracellular cyclic adenosine triphosphate and to inhibit IL-2 synthesis. All together these results suggest that several G proteins are involved in the transduction of the two signals necessary for T cell activation as well as in the negative regulation of IL-2 synthesis.
Human immune response to group A streptococcal carbohydrate (A-CHO). II. Antigen-independent stimulation of IgM anti-A-CHO production in purified B cells by a monoclonal anti-idiotopic antibody.
Authors: Bloem A , Zenke G , Eichmann K , Emmrich F 
Published: December 2022

Abstract
The paper describes the induction by a monoclonal anti-idiotopic antibody (anti-Id mAb) of specific antibody production to group A streptococcal carbohydrate (A-CHO) in purified human B cells of several unrelated individuals. The anti-Id mAb, designated 16F498 (anti-Id498), recognizes a recurrent idiotope (Id 498) associated with the combining site of human antibodies to N-acetyl-D-glucosamine (GlcNAc), the immunodominant group of A-CHO. Id498 is expressed on IgM anti-GlcNAc antibodies but does not occur on IgG antibodies with the same specificity. It occurs also on a minor population of IgM antibodies without specificity for A-CHO. Id498 was found in 19 of 27 sera from unselected healthy donors and thus seems to be frequently expressed within the adult B cell repertoire. The in vitro induction of anti-A-CHO antibodies was analyzed in human B cells extensively depleted for T cells. Specific antibody secretion required cross-linked anti-Id which was achieved by coupling the mAb to agarose beads. No antibody secretion could be induced by soluble anti-Id (1 and 10 micrograms/ml). An optimal response required soluble T cell-derived factors which were added as a mixture of recombinant interleukin 2 with a T cell hybridoma supernatant that augments B cell growth and differentiation. Under these conditions an antigen-independent specific increase of IgM anti-A-CHO production (2.6- to 10-fold, or up to 2000 ng/ml respectively) could be induced in blood B cell populations of four of six normal individuals expressing the Id498 at serum level.
Isolation and characterization of a complementary DNA expressing human U1 small nuclear ribonucleoprotein C polypeptide.
Authors: Yamamoto K , Miura H , Moroi Y , Yoshinoya S , Goto M , Nishioka K , Miyamoto T 
Published: December 2022

Abstract
A cloned complementary DNA, termed pS2, was isolated from a human fibroblast cDNA library in the bacteriophage expression vector lambda gt11 after screening with a patient's serum containing a high titer of anti-ribonucleoprotein (RNP) antibodies. A reasonable amount of cro-beta-galactosidase fusion protein (pS2EX) was obtained through subcloning of the pS2 insert into a plasmid expression vector pEX-2. Antibody against pS2EX (anti-pS2EX) was purified from this patient's serum by Sepharose 4B conjugated with pS2EX. Immunofluorescent staining of HeLa cells with anti-pS2EX antibody exhibited a typical speckled pattern in the interphase nuclei. In the immunoblot analysis, the anti-pS2EX antibody recognized the 22 kDa protein. Using immunoprecipitation of cell lysate and subsequent RNA analysis, anti-pS2EX antibody was shown to precipitate U1 RNP only. The reactivities of various anti-RNP sera to pS2EX correlated well with the positive reaction to C polypeptide in the immunoblot. These findings indicate that pS2 is a cDNA for C polypeptide of U1 snRNP. In the Northern blot using human RNA and radiolabeled pS2, a single band about 800 base was observed. The nucleotide sequence of pS2 showed no significant homologies to known proteins.
Comparison of phorbol ester/calcium ionophore and phytohemagglutinin-induced signaling in human T lymphocytes. Demonstration of interleukin 2-independent transferrin receptor gene expression.
Authors: Kumagai N , Benedict S H , Mills G B , Gelfand E W 
Published: December 2022

Abstract
The proliferation of human T lymphocytes is regulated, in part, by the coordinated expression of genes encoding T cell growth factor (interleukin 2 (IL-2), IL-2 receptors, and transferrin receptors (TFR). We examined the time course of accumulation of mRNA for these genes in T cells stimulated with the phorbol ester, phorbol 12,13-dibutyrate (PDB) and the calcium ionophore, ionomycin, and compared their expression to T cells stimulated with phytohemagglutinin. In cells treated with PDB/ionomycin, maximum expression was observed at 3 hr for IL-2 mRNA and at 6 hr for TFR mRNA, whereas the level of IL-2 receptor mRNA reached a peak 24 to 48 hr after stimulation. In phytohemagglutinin-stimulated T cells IL-2 mRNA was detectable within 3 hr but peaked later at 12 hr; the level of IL-2 receptor mRNA similarly peaked 24 to 48 hr later. Accumulation of TFR mRNA in phytohemagglutinin-stimulated T cells, however, was not detectable at 6 hr and reached a peak only between 12 to 24 hr. The early accumulation of TFR mRNA in PDB/ionomycin-stimulated T cells seemed, in part, independent of the interaction of IL-2 with its own receptor, because TFR mRNA was detectable as early as 1 hr after stimulation and addition of cycloheximide before addition of PDB/ionomycin did not abolish the PDB/ionomycin-induced accumulation of TFR mRNA. In addition, either PDB or ionomycin used alone induced the expression of TFR mRNA but not IL-2 mRNA. These results indicated that the combination of PDB/ionomycin accelerated the expression of IL-2 and TFR genes in T cells compared to phytohemagglutinin and triggered an IL-2-independent pathway for the induction of TFR mRNA.
Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice.
Authors: Miller B J , Appel M C , O'Neil J J , Wicker L S 
Published: December 2022

Abstract
The nonobese diabetic mouse is a model of spontaneous type I diabetes mellitus. It is possible to induce diabetes in young, irradiated nonobese diabetic mice by using adoptive transfer of splenocytes or splenic T cells obtained from diabetic donors. This study demonstrates that the induction of diabetes in the adoptive transfer system is dependent on both the L3T4+ and Lyt-2+ subsets of T cells. Neither of these T cell subsets alone mediates the development of severe insulitis or diabetes when adoptively transferred to young, irradiated recipients. In addition, we show that both the L3T4+ and Lyt-2+ subsets must be obtained from diabetic donors in order to transfer diabetes; neither subset can be replaced with cells obtained from young, nondiabetic donors.
Monoclonal anti-idiotopic antibodies against myasthenia-inducing anti-acetylcholine receptor monoclonal antibodies. Preponderance of nonparatope-directed antibodies affecting antigen binding.
Authors: Agius M A , Geannopoulos C J , Fairclough R H , Richman D P 
Published: December 2022

Abstract
To analyze components of the idiotypic network in experimental autoimmune disease, we produced 17 isogeneic anti-idiotopic monoclonal antibodies (anti-Id) against two experimental autoimmune myasthenia gravis-producing anti-acetylcholine receptor (anti-AChR) monoclonal antibodies. We studied the binding of five of the anti-Id to the anti-AChR monoclonal antibodies bearing the complementary idiotopes (Id-mAb). They bound with Kd values ranging from 0.06 to 0.86 nM, values comparable to those of Id-mAb:AChR complexes (0.26 and 0.34 nM). All of the anti-Id tested moderately inhibited the binding of AChR to Id-mAb, whereas for each anti-Id, AChR either strongly inhibited anti-Id binding or had no effect on anti-Id binding. Hence, the inhibition of Id-mAb:AChR binding by anti-Id was not reciprocal with the inhibition of anti-Id:Id-mAb binding by AChR. For each anti-Id, the relative affinities of anti-Id and AChR for Id-mAb together with the lack of symmetry of inhibition by anti-Id compared to inhibition by AChR indicate that these two "ligands" are not competitive inhibitors. Consequently, anti-Id and AChR do not bind to overlapping sites on the Id-mAb, suggesting that the observed inhibition is mediated allosterically. This may be a common mechanism of anti-Id:Id binding, which would have important implications for the mechanism of anti-Id-induced suppression.
Monoclonal autoantibody recognizing a unique set of small nuclear ribonucleoprotein complexes.
Authors: Winkler A , Watson-McKown R , Wise K S 
Published: December 2022

Abstract
A murine IgG2a, kappa-monoclonal autoantibody (mAb) F78 is described that recognizes a novel epitope associated with small nuclear ribonucleoprotein complexes (snRNP). F78 selectively immunoprecipitated a unique pattern of small nuclear RNA (U1, U2, and U4 to U6) characterized by a marked depletion of U1 and an elevated proportion of U2 compared with known patterns immunoprecipitated by previously described anti-RNP (2.73) and anti-Sm (7.13, Y12) mAb. Analysis of immunoprecipitated RNA from extracts previously cleared with mAb F78 and probed with anti-RNP mAb 2.73 further indicated the presence of two distinct subsets of U1. Immunoblots of whole cell extracts separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) without heating showed that F78 selectively bound to a trypsin-sensitive component of apparent m.w. greater than 120,000 which was decreased in size following RNase A treatment. The anti-Sm mAb, but not the anti-RNP mAb, also recognized this component in unheated samples. Heating before SDS-PAGE resulted in abrogation of binding to the F78 epitope. Immunoprecipitation of unlabeled or [35S]methionine-labeled cell extracts with F78 revealed the presence of most snRNP peptides, but the absence of peptide C and the 68,000 m.w. component, known to be selectively associated with U1-specific snRNP. Two-dimensional SDS-PAGE analysis of F78 immunoprecipitates confirmed that the epitope recognized by this mAb resides on a heat-dissociable complex containing snRNP-related peptides B, B', D, E, F, and G, but lacking U1-associated peptides. F78 mAb therefore defines a subset of snRNP which lack anti-RNP associated U1 RNA as well as peptides known to be selectively associated with this RNA species. It apparently recognizes an epitope associated with an assembled form of these particles and may be useful in examining structures involved in RNA processing.
Isolation of T cell line capable of protecting mice against collagen-induced arthritis.
Authors: Kakimoto K , Katsuki M , Hirofuji T , Iwata H , Koga T 
Published: December 2022

Abstract
A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.
In vivo tolerance induction and associated cytokine production by subsets of murine CD4+ T cells.
Authors: Chu E B , Hobbs M V , Ernst D N , Weigle W O 
Published: December 2022

Abstract
Male BXSB mice develop lupus-like disease and die early in life (4 to 5 mo) whereas female mice do not. Others have demonstrated that CD4+ cells from male mice support B cell resistance to tolerance induction to human gamma-globulin (HGG). In this study, male and female mice tolerized at 2 mo of age with deaggregated HGG and subsequently immunized with HGG in comparison with mice immunized only were tested for anti-HGG Ab responses. CD4+ cells from draining lymph nodes of these mice were tested in culture for proliferation and production of cytokine mRNA and protein in response to HGG plus APC. Tolerized male but not female mice produced anti-HGG Abs of both the IgG1 and IgG2a isotypes. HGG-stimulated CD4+ cells from immunized male and female mice that were not tolerized produced IL-2, IL-4, IL-5, IFN-gamma, and TNF-beta mRNA as well as IL-2 and IL-4 protein, whereas tolerized, immunized mice of both sexes failed to proliferate or produce either IL-2 or IL-4 or express any cytokine mRNA in response to HGG in vitro. A resistance in tolerance induction in male mice, as determined by anti-HGG Abs, was also observed at 3 mo of age. Although a resistance to tolerance was also seen in terms of proliferation in the 3-mo-old males, production of IL-2 or IL-4 protein was still not observed. Thus, all T cell subsets identified by cytokine expression profiles were tolerized not only from females but also from males, of which the latter appeared to show some resistance to tolerance induction.
Transfection of TCR alpha-chains into suppressor and T helper cell hybridomas. Production of suppressor factors with predicted antigen specificity.
Authors: Kuchroo V K , Byrne M C , Greenfield E , Whitters M J , Nalefsky E A , Rao A , Collins M , Dorf M E 
Published: December 2022

Abstract
Conditioned medium from Ag-specific suppressor T cell hybridomas contains soluble factors (TsF) that modulate immune responses in an Ag-specific manner. We previously generated a series of TCR-alpha- and TCR-beta- expression variants from a 4-hydroxy-3-nitrophenyl acetyl (NP)-specific inducer suppressor T cell hybridoma and demonstrated that loss of TCR alpha-chain mRNA, but not TCR-beta chain mRNA, was accompanied by concomitant loss of suppressor bioactivity. Suppressor factor bioactivity was restored by expression of TCR alpha-chain cDNA, suggesting that the TCR alpha-chain plays a critical role in Ag-specific suppressor cell function. We have now transfected TCR alpha-chain from a Th cell clone specific for arsanylated peptides plus I-Ad into a TCR-alpha- derivative of an NP-specific inducer suppressor T cell hybridoma. The transfectants expressed a new hybrid TCR-alpha beta complex and produced soluble factors that suppressed azobenzenearsonate hapten (ABA) but not NP delayed-type hypersensitivity responses. These supernatants mediated suppression of the induction, but not the effector phase of the delayed-type hypersensitivity reaction. In reciprocal experiments we transfected a TCR alpha-chain from an NP-specific suppressor T cell hybridoma into a TCR-alpha- hybridoma derived from the ABA-specific Th cell hybridoma. The NP-specific TCR alpha-chain was expressed in the Th cell hybridoma, but the supernatant from this transfectant did not suppress DTH responses to either NP or ABA. However, the latter supernatants, when combined with cell lysates derived from a TCR-alpha- Ts hybridoma, specifically suppress NP DTH responses. These data are consistent with the interpretation that TCR alpha-chain imparts Ag specificity to the suppressor molecule and a second, yet undefined, component produced by the Ts hybridoma controls the immunoregulatory bioactivity.
Met-enkephalin-containing peptides encoded by proenkephalin A mRNA expressed in activated murine thymocytes inhibit thymocyte proliferation.
Authors: Linner K M , Quist H E , Sharp B M 
Published: December 2022

Abstract
Murine thymocytes activated with the mitogen Con A express proenkephalin A mRNA (PEA mRNA) and met-enkephalin and/or met-enkephalin-containing peptides ("enkephalins"). This Con A-induced expression of PEA mRNA is modulated by the delta opioid receptor agonist, deltorphin I, in a biphasic, dose-dependent manner. That is, 10(-13) M to 10(-11) M deltorphin enhanced PEA mRNA expression 3- to 3.5-fold over the level induced by Con A alone, and 10(-9) M to 10(-7) M deltorphin inhibited it 40 to 70%. delta opioid receptor antagonists recognizing the delta-2 (naltrindole (NTI) and naltriben (NTB)), but not the delta-1 (7-benzylidenenaltrexone (BNTX)), subtype of opioid receptor described in brain, reversed both the enhancing and inhibiting effects of deltorphin on Con A-induced PEA mRNA expression. In addition, the delta-2 receptor-specific antagonists, NTI and NTB, directly inhibited Con A-induced PEA mRNA expression. The function of the enkephalins expressed by thymocytes was examined by using 1) delta opioid receptor antagonists, 2) PEA mRNA-specific antisense cDNA, and 3) Ab to met-enkephalin, and measuring cell proliferation. All three reagents caused enhancement of Con A-induced proliferation, with effects ranging from two- to fourfold over the response to Con A alone. Again, the delta-2 subtype-specific antagonists, NTI and NTB, were functional and the delta-1 subtype-specific antagonist, BNTX, was not. The PEA mRNA-specific antisense cDNA blocked translation but not transcription of PEA mRNA. The data suggest that 1) endogenous enkephalins induced in thymocytes modulate their own expression through delta-2-like opioid receptors, and 2) these endogenous enkephalins function to inhibit the proliferation of activated thymocytes.
Effect of IL-12 on immune suppression and suppressor cell induction by ultraviolet radiation.
Authors: Schmitt D A , Owen-Schaub L , Ullrich S E 
Published: December 2022

Abstract
The carcinogenic potential of UV radiation (the primary cause of nonmelanoma skin cancer) is associated with its ability to suppress cell-mediated immune responses. Previous studies have shown that this UV-induced immune suppression is caused by the secretion of immunosuppressive cytokines such as IL-10. Because the effects of IL-10 on the immune response are countered by IL-12, we injected irradiated mice with IL-12 to determine whether it could overcome UV-induced immune suppression. Administration of IL-12 blocked the suppression of delayed-in-time hypersensitivity reactions observed in UV-irradiated animals. Moreover, IL-12 prevented the induction of suppressor T cells, in that adoptive transfer of spleen cells from UV-irradiated mice treated with IL-12 had no effect on the immune response of the recipient mice, whereas transfer of spleen cells from UV-irradiated mice treated with the vehicle inhibited the immune response. In addition, IL-12 neutralized the activity of UV-induced suppressor T cells. Although the adoptive transfer of UV-induced suppressor T cells from irradiated mice suppressed the immune response of the recipient mice, treatment of the recipient mice with IL-12 following the adoptive transfer overcame the immune suppression. The results of these experiments demonstrate that IL-12 can overcome UV-induced immune suppression by preventing the induction of, as well as neutralizing the activity of pre-formed suppressor T cells.