bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular analysis of the dissociation between IL-2 production and proliferation in a response of a T cell clone to the antigen presented by B cells.
Authors: Kakiuchi T , Mizuguchi J , Nariuchi H 
Published: December 2022

Abstract
Using B cells as APC, antigen specific responses of two murine T cell clones, 34-7F and 35-8H, were analyzed. 34-7F cells produced IL-2 but failed to proliferate, whereas 35-8H cells both produced IL-2 and proliferate. The antigenic stimulation increased intracellular free Ca2+ concentration in both clones, but enhanced inositol phospholipid metabolism only in 35-8H cells. The treatment of 34-7F cells with PMA, an activator of protein kinase C, synergized with the antigenic stimulation to induce the proliferation of the T cells. Thus, the failure of 34-7F cells to proliferate in the Ag response appears to result from the absence of an increase in inositol phospholipid metabolism. The absence is likely due to the defect in B cells as APC, inasmuch as the antigenic stimulation of 34-7F cells with whole spleen cells induced increases in inositol phospholipid metabolism and proliferation. The PMA treatment synergized with the Ag on B cells to enhance IL-2R expression, which was not inhibited by the addition of nifedipine, a calcium channel blocker. The agent inhibited the IL-2 production. Taken together, the results in the present experiments suggest the association of IL-2 production with increases in intracellular free Ca2+ concentration but not in inositol phospholipid metabolism, and that of IL-2R expression with increases in the metabolism but not in intracellular free Ca2+ concentration.
Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent-strain spleen cells. II. Evidence for an Hh-1 antigen-specific tolerization.
Authors: Kosmatopoulos K , Scott-Algara D , Halle-Pannenko O 
Published: December 2022

Abstract
Lethally irradiated F1 mice reject bone marrow graft from H-2b parents. In a previous paper we showed that pretreatment of F1 hybrid with H-2b parental spleen cells abrogates this hybrid resistance (HR) to parental bone marrow growth by inducing a Thy-1+Lyt-1+2- nylon-adherent suppressor cell. We studied the mechanism of induction of this suppressor cell. Two hypotheses were tested; both were based on the observation that parental spleen cells when injected into a F1 hybrid, recognize the alloantigens of the opposite parent and proliferate; the proliferation of these Hh-1+ cells may result in an overload of the pretreated F1 hybrids with Hh-1 Ag, and in the development of a graft-vs-host reaction that is followed by a non-specific immunodeficiency (GVHID). Thus abrogation of HR could be due to either a tolerization with high doses of Hh-1 Ag or the GVHID. Our results show that abrogation of HR does not correlate with the GVHID because 1) it is induced after pre-treatment with H-2b parental cells only, whereas GVHID is observed after injection with cells from either of the two parents; and 2) it is induced in several conditions where GVHID does not occur; after pre-treatment with 1000-rad-irradiated or T-cell depleted or only class I incompatible spleen cells or with spleen cells from nude parents as well as after pre-treatment with H-2b bone marrow cells. HR is overcome by the injection of H-2Db homozygous or of cross-reactive H-2Ds homozygous cells only. However, although pretreatment with H-2Db homozygous spleen cells is necessary, it is not sufficient for an efficient overcoming of HR. Indeed enhancement of H-2b bone marrow growth after pre-treatment with 1000-rad-irradiated, T-cell depleted or nude parent spleen cells is very short-lasting and never reaches the level observed after pre-treatment with normal spleen cells. We conclude that inhibition of HR in F1 hybrids pretreated with parental spleen cells is not a consequence of a GVHID but of a specific tolerization with Hh-1 Ag; however, the HR is inhibited more consistently when inoculum used for the pretreatment contains fully immunocompetent T cells. The role of the immunocompetent parental T cells in abrogation of HR is discussed.
Class I MHC-restricted recognition of cells expressing a gene encoding a 41 amino acid product of the influenza hemagglutinin.
Authors: Sweetser M T , Braciale V L , Braciale T J 
Published: December 2022

Abstract
Class I H-2Kd-restricted influenza hemagglutinin (HA)-specific CTL recognize two immuno-dominant sites as represented by synthetic peptides spanning epitopes located in the HA1 and hydrophobic transmembrane domains of the influenza HA. Using a vaccinia virus recombinant expression system, we have examined CTL recognition of HA deletion mutants expressed in target cells. We have demonstrated that a truncated influenza HA gene encoding only the transmembrane anchor region containing a class I recognition site and a short segment of the cytoplasmic tail of the HA can be efficiently presented to class I CTL. These results set the stage for detailed analyses of the intracellular events associated with Ag presentation to class I CTL and offer novel possibilities for future vaccine design.
Subtypes of helper cells. Non-inflammatory type 1 helper T cells.
Authors: Wong R L , Ruddle N H , Padula S J , Lingenheld E G , Bergman C M , Rugen R V , Epstein D I , Clark R B 
Published: December 2022

Abstract
Class II MHC-restricted T cells recently have been characterized as being either type 1 (Th1) or type 2 (Th2) based on their ability to both secrete different lymphokines and perform different functions. Characterization of these subtypes to date have indicated that Th1 cells secrete IL-2, IFN-gamma, lymphotoxin, and IL-3, whereas Th2 cells secrete IL-4, IL-5, and IL-3. Functionally, Th1 cells mediated cytotoxicity and delayed-type hypersensitivity, and have been termed "inflammatory cells," whereas Th2 cells mediate helper function for Ig secretion and have been termed, "regulatory cells." We now present evidence that not all Th1 clones are inflammatory and capable of mediating cutaneous delayed-type hypersensitivity. We have generated a number of myelin basic protein-specific Th1 clones that do not mediate swelling when injected together with myelin basic protein directly into the footpads of syngeneic mice. These results suggest that Th1 cells can be further subdivided based on their ability to mediate delayed-type hypersensitivity, and that the Th1/Th2 characterization of Th cells may be insufficient to adequately characterize all functional subtypes of class II MHC-restricted T cells.
Characterization of human peripheral lymphocytes expressing the CD3-gamma/delta complex with anti-receptor monoclonal antibodies.
Authors: Faure F , Jitsukawa S , Triebel F , Hercend T 
Published: December 2022

Abstract
Three mAb, anti-Ti gamma A, anti-TCR delta 1, and anti-delta TCS1, have been developed against the CD3-associated gamma/delta molecular complex. One of this antibody anti-Ti gamma A is specific for an epitope encoded by the V9 gamma-gene. The two others react with the delta-chain but their fine epitopic specificity has not been characterized previously. In the present study, we have compared the surface expression of these three antigenic determinants on 27 cloned and 5 polyclonal CD3+ TCR gamma/delta + cell lines derived from human peripheral blood of 13 distinct individuals. It was found that all CD3+ TCR alpha/beta- clones and polyclonal cell lines tested were recognized by anti-TCR delta 1. In contrast, only a fraction of both clones and cell lines reacted with either anti-Ti gamma A or anti-delta TCS1 mAb. In fact reactivity of the latter reagents was found to be mutually exclusive on the cell panel. Northern blot analysis of RNA extracted from a series representative clones showed a positive correlation between the surface expression of the delta TCS1 epitope and the transcription of the V-delta gene isolated from the IDP2 cell line. These data support the view that anti-TCR delta 1 can be used to positively define the entire TCR gamma/delta+ fraction. Moreover, the reciprocal reactivity of anti-delta TCS1 and anti-Ti gamma A on cultured cell lines suggests that these reagents should delineate in human peripheral blood distinct, essentially non-overlapping, subsets. Taken together, the present results indicate that the complementary use of these three antibodies will be helpful to further characterize the TCR gamma/delta + peripheral lymphocyte fraction.
Pre-exposure of human B cells to recombinant IL-1 enhances subsequent proliferation.
Authors: Freedman A S , Freeman G , Whitman J , Segil J , Daley J , Nadler L M 
Published: December 2022

Abstract
The reported effects of the monocyte-derived cytokine IL-1 on human B lymphocytes are both varied and controversial. IL-1 has been reported to augment both proliferation and Ig secretion of previously activated human B cells. In the present study highly purified splenic B cells were cultured with rIL-1 before, simultaneously with, and after the addition of the polyclonal B cell mitogen, anti-Ig. rIL-1 had no significant effect on B cell proliferation when added simultaneously with or after B cell activation with anti-Ig. However, incubation of splenic B cells with rIL-1 for 24 h before stimulation with anti-Ig appeared to enhance mitogenesis. With the observation that rIL-1 exerted effects on resting B cells, the effect of rIL-1 on several events which accompany B cell activation was examined. rIL-1 failed to stimulate RNA synthesis, effect increases in cell size or intracellular Ca2+ levels, or lead to the hyperexpression of MHC class II or B cell activation Ag. These studies suggest that rIL-1 does not activate B cells but primes them to respond to subsequent activation.
Cholera toxin discriminates between murine T lymphocyte proliferation stimulated by activators of protein kinase C and proliferation stimulated by IL-2. Possible role for intracellular cAMP.
Authors: Kim D K , Nau G J , Lancki D W , Dawson G , Fitch F W 
Published: December 2022

Abstract
The regulation of the activation of T lymphocyte proliferation is not well understood. It is known that the tumor promoter, PMA, which activates protein kinase C (PKC), can induce the proliferation of several murine CTL clones; in combination with calcium ionophores, which raise the level of intracellular Ca2+, PMA can also stimulate the proliferation of several HTL clones. Activation of the TCR is believed to result in the liberation of diacylglycerol, which is an activator of PKC, and inositol 1,4,5-trisphosphate, which stimulates an increase in intracellular levels of calcium. We now report that pretreatment with cholera toxin (CT) inhibits the proliferation of murine T cell clones stimulated through the TCR/CD3 complex. In addition, CT-pretreatment blocks the proliferation of CTL clones activated with PMA or of HTL clones activated with PMA + calcium ionophore. In contrast, CT-pre-treatment inhibits much less effectively (100- to 1000-fold) the proliferation of these T cell clones stimulated with IL-2. Furthermore, activators of PKC, but not IL-2, potentiate the CT-induced cAMP elevation in T cell clones. The ability of CT to inhibit much more effectively the proliferation triggered by putative activators of PKC than that induced by IL-2 may be mediated by cAMP-dependent mechanisms.
Expression of CD5 regulates responsiveness to IL-1.
Authors: Nishimura Y , Bierer B E , Burakoff S J 
Published: December 2022

Abstract
The role of the CD5 surface molecule in T cell responsiveness to IL-1 was examined. A CD5-mutant Jurkat cell line was generated from a CD5+ parent cell line. This CD5- mutant subclone was infected with a defective retrovirus containing the CD5 cDNA and/or the neo gene encoding G418 resistance. The CD5+ wild type Jurkat produced IL-2 in response to anti-CD3 mAb, OKT3, cross-linked to a solid surface. IL-2 production was enhanced by co-culture with IL-1 or anti-CD5 Mab. Neither the CD5- mutant nor the CD5- G418-resistant infectant responded to anti-CD5 mAb or to IL-1. Responsiveness to IL-1 was restored by cell surface expression of CD5 in the CD5+ infectant. Both the CD5+ wild type Jurkat and the CD5+ infectant responded equivalently to purified IL-1, IL-1 alpha and rIL-1 beta. Optimal concentrations of IL-1 and anti-CD5 mAb had an additive effect on the enhancement of IL-2 production stimulated with cross-linked anti-CD3 mAb suggesting that IL-1 and CD5 act through distinct, complementary pathways to augment T cell activation. The correlation of CD5 expression and specific binding of rIL-1 beta was examined in these cell lines. Both the specific binding (at 4 degrees C) and subsequent internalization (at 37 degrees C) of 125I labeled rIL-1 beta was equivalent in the CD5+ infectant and the CD5+ wild type Jurkat cell, whereas specific binding of 125I-labeled rIL-1 beta was markedly decreased in the CD5-G418-resistant infectant. These observations strongly suggest that cell surface expression of CD5 regulates binding of and responsiveness to IL-1.
Characterization of protein kinase C and its isoforms in human T lymphocytes.
Authors: Beyers A D , Hanekom C , Rheeder A , Strachan A F , Wooten M W , Nel A E 
Published: December 2022

Abstract
Protein kinase C (PKC) regulates numerous T cell functions and is present in abundance in normal human T cells and certain T cell lines. Although crude Triton X-100 soluble material obtained from T cell pellets contains minimal PKC activity, DEAE chromatography revealed that 12 to 37% of cellular PKC was membrane associated, probably due to removal of an inhibitor through column chromatography. As in other tissues, PKC from lymphoid tissue was phospholipid and Ca2+ dependent and diolein reduced the Ca2+ requirements for enzyme activity. Hydroxylapatite chromatography revealed that T cells possess two major peaks of PKC activity. Although, the enzyme in these peaks had similar m.w. and identical iso-electric mobility, the proteins differed with respect to their autophosphorylation sites and immunoreactivity toward an isoform specific antibody. Furthermore, differences in their activities in the presence of phospholipid, diolein, and limiting amounts of Ca2+ imply that these isoforms may be differentially activated. We discuss optimal conditions for activation of PKC and its isoforms for study of T lymphocyte cellular function.
Neutrophils and mast cells. Comparison of neutrophil-derived histamine-releasing activity with other histamine-releasing factors.
Authors: White M V , Kaplan A P , Haak-Frendscho M , Kaliner M 
Published: December 2022

Abstract
Human neutrophil-derived histamine-releasing activity (HRA-N) was partially purified and found to contain a heat-stable 1400 to 2300-Da fraction which caused human basophils and rat basophil leukemia cells (RBL) to degranulate. The capacity of HRA-N to activate basophils was not related to the gender or atopic status of the basophil donor, but was related to anti-IgE responsiveness. Several lines of evidence suggest that HRA-N and anti-IgE induce histamine release through distinctly different mechanisms: 1) the time course of HRA-N- and anti-IgE-induced RBL histamine release are different; 2) HRA-N causes histamine release from RBL with and without surface-bound IgE; 3) lactic acid stripping of IgE from human basophils reduces anti-IgE-induced histamine release, but has no consistent effect on HRA-N-induced histamine release; and 4) passive sensitization of lactic acid-stripped basophils with IgE restores anti-IgE-induced histamine release but not HRA-N-induced histamine release. Several histamine-releasing factors (HRF) were compared with HRA-N. Human nasal HRF (HRF-NW, crude and partially purified fractions of 15 to 30, 3.5 to 9, and less than 3.5 kDa), like HRA-N, caused equal histamine release from both native and IgE-sensitized RBL. However, only the 15- to 30-kDa fraction caused histamine release from human basophils in the doses tested. Mononuclear cell HRF (HRF-M, crude and a partially purified 25 kDa Mr fraction) and platelet HRF (HRF-P, crude preparation) failed to cause histamine release from either native or IgE-sensitized RBL but caused 30 +/- 5.5% and 20 +/- 10% net histamine release from human basophils, respectively. HRA-N and HRF-NW were both stable to boiling. These data, taken together, suggest that the capacity of HRA-N to induce RBL and human basophil histamine release and of HRF-NW to stimulate RBL histamine release is independent of IgE. The data further suggest that HRA-N and HRF-NW can be distinguished by size, and that they both differ from mononuclear cell HRF and platelet HRF. Thus, it appears that inflammatory cells generate a family of distinct HRF.
Lineage and stage specificity of isotype switching in humans.
Authors: Borzillo G V , Cooper M D , Bertoli L F , Landay A , Castleberry R , Burrows P D 
Published: December 2022

Abstract
The lineage and stage specificity of human isotype switch recombination was investigated by examining the IgH gene configuration in 61 hemopoietic malignancies representing different stages of B and T cell development. An unexpectedly high frequency (20%) of IgM-producing B cell leukemias and lymphomas had undergone CH gene rearrangements and deletions consistent with attempted switch recombination. These CH gene alterations were found on productive, non-productive, and 14q+ chromosomes. These data support the concept of a non-specific (common) switch recombinase activity that is often ineffective. No evidence of such switch recombination was found in 25 mu- or mu+ pre-B cell leukemias with the single exception of a mu- pre-B leukemia in which subsets of the cells were producing gamma- or alpha-H chains. The switch recombinase activity gamma- or alpha-H chains. The switch recombinase activity may be restricted to the B cell lineage, inasmuch as CH gene deletions were not observed in T lineage malignancies.
Defective E beta expression in three mouse H-2 haplotypes results from aberrant RNA splicing.
Authors: Tacchini-Cottier F M , Jones P P 
Published: December 2022

Abstract
The molecular basis for the defective expression of the mouse class II E beta genes in the H-2w17, H-2q, and H-2f haplotypes has been examined. The results of nuclear run-on transcription and S1 nuclease digestion assays demonstrate that E beta transcription is normal in these haplotypes. Northern blot analyses reveal reduced amounts of E beta RNA of both normal and aberrant size in the w17 and q haplotypes; an even more reduced level of E beta RNA of normal size was detected in the f haplotype. In the preceding study, we reported that the only defect detected in the E beta w17 gene is a single nucleotide insertion in the 5' RNA splice site of the first intervening sequence. S1 nuclease analysis of E beta w17 RNA indicates that splicing at this site is aberrant. One major cryptic RNA splice site is used, leading to reduced amounts of aberrantly processed RNA. Limited use of the mutated splice site and of a second cryptic site also is detected. In all three cases, stop codons in the resulting RNA would prevent their translation. The molecular defect in E beta q appears identical to that of E beta w17. In the f haplotype, even more reduced levels of E beta RNA of both normal and aberrant sizes are found. We thus show that in the three defective E beta alleles, two distinct defects are responsible for the absence of E beta protein synthesis; both of these defects affect RNA processing.
T cell activation by preformed, long-lived Ia-peptide complexes. Quantitative aspects.
Authors: Watts T H 
Published: December 2022

Abstract
Planar membrane-bound complexes between a fluorescent peptide, FITC-OVA(323-339), and the class II MHC Ag, I-Ad, were analyzed by fluorescence microscopy and in biological assays to determine the optimum distance between peptide-Ia complexes required for maximum activation of IL-2 production by the Th cell hybridoma DO-11.10. Optimum responses were obtained when the average distance between peptide-Ia complexes was of the order of 200 A. This implies that T cell activation by Ag-MHC requires cross-linking of the TCR via closely packed Ag-MHC complexes. The same dose response curve to the preformed complexes was obtained whether one used a fixed concentration of Ia and varied the peptide concentration or a fixed concentration of peptide and varied the Ia concentration. In both cases there was a linear relationship between the number of peptide-Ia complexes and the response of the T cells. The association between Ia and peptide in vitro is an inefficient process, requiring prolonged incubation and a large excess of peptide over Ia. Once formed, however, the complex is extremely stable with no detectable dissociation at neutral pH after days at 4 degrees C. With several different preparations of Ia it was found that only about 10 to 20% of the purified Ia is capable of forming the long-lived complex with peptide.
Avidity dictates the lytic capacity of human cytolytic T lymphocyte clones with similar fine specificity against murine cells expressing HLA-B27 antigen.
Authors: Calvo V , Rojo S , Aparicio P , Galocha B , López de Castro J A 
Published: December 2022

Abstract
The role of the avidity of human CTL in the recognition and lysis of murine P815 cells expressing HLA-B27.1 Ag has been examined. Seven B27-specific alloreactive CTL clones were tested for their ability to lyse a B27.1+-P815 transfectant clone 1-7E, obtained after cotransfection of P815-HTR cells with HLA-B27.1 and human beta 2-microglobulin genes. The expression level of HLA-B27.1 on 1-7E cells was comparable to that on a human lymphoblastoid cell line, as determined by flow cytometry. Of the seven CTL clones used, CTL 1, 26, and 29 displayed the same fine specificity as established with a panel of target cells expressing six structurally different HLA-B27 variants. However, CTL 1 and 29 were of higher avidity than CTL 26, in that the lysis of human target cells by only this latter clone was inhibited by an anti-CD8 mAb. Based on the same criteria, CTL 2, 15, and 48 possessed the same or very similar fine specificity, but CTL 48 was of higher avidity than CTL 2 or 15. The seventh clone, CTL 40, was of a different fine specificity and its lysis of human target cells was also inhibited by the same anti-CD8 mAb. Only those clones whose lysis of human targets could not be inhibited by anti-CD8 antibody were able to lyse the 1-7E murine transfectants. These results indicate that, for human CTL clones with identical or very similar fine specificity, only those of higher avidity are able to lyse P815 murine cells expressing the HLA-B27 antigen. The lysis of HLA-B27.1+-murine transfectants by relevant clones was inhibited by anti-CD8 antibody. This result strongly suggests that the relative contribution of CD8 in stabilizing the interaction between human CTL and HLA-B27+-murine target cells is more significant than with human target cells.