bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presentation of anti-idiotypic antibody is sensitive to ionizing radiation.
Authors: Johnson-Léger C A , Dean C J 
Published: January 2023

Abstract
We have been investigating the generation of specific immune responses using monoclonal anti-idiotypic Abs (Ab2) as surrogate tumor Ag. We have prepared a series of idiotypic mAbs (Ab1) from CBH/cbi rats bearing the syngeneic sarcoma HSN and have used these Ab1 to generate autologous Ab2. By using the autologous Ab2 as Ag, we have isolated T cell lines from CBH/cbi rats that proliferate specifically in the presence of the Ab2, with spleen cells as APC. Specific proliferation of the T cells was prevented if the spleen cells used for presentation were irradiated with conventional doses of x-rays (1000 rad) just before use. Titration of the radiation response showed that the capacity of the spleen cells to present Ag decreased exponentially with x-ray doses of up to 100 rad, at which dose presentation was virtually abolished. The same irradiated spleen cells were fully competent to present OVA to CBH/cbi-derived rat T cell lines specific for this Ag. Preincubating the APC with Ag before irradiation abrogated the effect of x-irradiation on the presentation of Ab2. We conclude that, in this rat system, the presentation of autologous Ab2 is highly sensitive to the effects of low doses of x-rays. The clinical significance of these findings is discussed.
Extrusion of the P glycoprotein substrate rhodamine-123 distinguishes CD4 memory T cell subsets that differ in IL-2-driven IL-4 production.
Authors: Witkowski J M , Li S P , Gorgas G , Miller R A 
Published: January 2023

Abstract
Approximately 25% of T cells in young mice are able to extrude the fluorescent P glycoprotein substrate Rhodamine-123 (R123), and these R123low cells are present within the naive and memory cell populations of both CD4 and CD8 type. The proportion of R123low T cells increases with age to approximately 60% in mice older than 18 mo of age. CD4 memory T cells from young mice secrete more IL-4 compared with cells from old donors when activated by anti-CD3 and further cultured for 7 to 10 days in the presence of IL-2. To determine whether this age-related decline in IL-4 production was related to the parallel accumulation of R123low T cells within the CD4 memory subset, we compared IL-4 production in cell preparations enriched for R123high and R123low cells by electronic cell sorting. IL-2-driven IL-4 production by CD3-activated CD4 memory cells was found to be limited almost entirely to the R123high subset, i.e., the subset that declines with age. Proliferation under these culture conditions also declined with age and was also much more vigorous in R123high than in R123low cells. Not all R123low T cells, however, were resistant to IL-2-dependent proliferation and differentiation: limit dilution analyses showed nearly equal proportions of Con A-responsive proliferative and cytotoxic clones within the R123high and R123low subsets of CD8 naive cells. These data show that P glycoprotein-mediated extrusion of R123 delineates CD4 memory T cell subsets that differ in function.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidermal cell presentation of tumor-associated antigens for induction of tolerance.
Authors: Tan K C , Hosoi J , Grabbe S , Asahina A , Granstein R D 
Published: January 2023

Abstract
Intravenous administration of hapten-coupled epidermal cells (EC) induces tolerance in mice. To assess the relevance of this observation to cutaneous tumors, the ability of EC to induce tolerance to the S1509a spindle cell tumor (H-2a) was examined. ECs were prepared from CAF1 (H-2a/d) mice and the supernatant from a freeze-thaw lysate of S1509a cells was used as a source of soluble tumor-associated Ag (TAA). ECs were incubated in TAA or medium alone followed by washing. Two hundred thousand TAA-pulsed ECs, non-TAA-pulsed ECs, or TAA-pulsed ECs killed by freeze-thawing were injected i.v. into groups of CAF1 mice. To determine whether this regimen induced tolerance, a tumor-specific delayed-type hypersensitivity (DTH) response was measured in mice subsequently immunized to the S1509a tumor. To assess the degree of immunity induced in these animals, ECs were prepared and deleted of Thy-1-bearing cells by Ab and complement-mediated lysis. These cells were then pulsed with TAA and 5 x 10(5) were injected into the right hind footpad of each mouse. Footpad swelling was assessed at 24 to 48 h as a measure of the DTH. Mice primed i.v. with viable TAA-pulsed EC but not killed TAA-pulsed EC demonstrated a greatly suppressed DTH response. Other experiments demonstrated that exposure of EC to a dose of ultraviolet radiation (200 J/m2), which inhibits the ability of these cells to induce immunity by subcutaneous injection either before or after TAA pulsing, did not prevent induction of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
Role and effect of TNF-alpha in experimental visceral leishmaniasis.
Authors: Tumang M C , Keogh C , Moldawer L L , Helfgott D C , Teitelbaum R , Hariprashad J , Murray H W 
Published: January 2023

Abstract
TNF-alpha has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. To determine the role of TNF-alpha in L. donovani-infected BALB/c mice, we measured TNF-alpha levels and treated mice with either anti-TNF-alpha antiserum or TNF-alpha. TNF-alpha activity in infected livers was increased by 2.7-fold 2 wk after challenge and by 5.5-fold at wk 8. In parallel, although control mice acquired resistance by wk 4 and resolved infection by wk 8, liver parasite burdens steadily increased in anti-TNF-alpha-treated animals. Hepatic granuloma formation, however, was not impaired by anti-TNF-alpha. Endogenous TNF-alpha levels provoked by L. donovani appeared sufficient and optimal because exogenous TNF-alpha administration had no beneficial effect on established infection and continuous high-dose treatment impaired antileishmanial activity. Thus, although not required for granuloma formation, endogenous TNF-alpha appears to be critical to both initial acquisition of resistance to L. donovani and resolution of experimental visceral infection.
Activation of protein kinase C down-regulates leukotriene C4 synthase activity and attenuates cysteinyl leukotriene production in an eosinophilic substrain of HL-60 cells.
Authors: Ali A , Ford-Hutchinson A W , Nicholson D W 
Published: January 2023

Abstract
An eosinophilic substrain of HL-60 cells (HL-60#7) predominantly synthesized cysteinyl leukotrienes after stimulation with the calcium ionophore A23187. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) specifically attenuated cysteinyl leukotriene production without affecting the biosynthesis of non-cysteinyl leukotrienes. The inhibition of cysteinyl leukotriene biosynthesis was prevented only by specific PKC inhibitors (staurosporine and bisindolylmaleimide) but not by inhibitors of tyrosine kinases (genistein, tyrphostin 47, and herbimycin A), protein kinase A (KT5720), or the oxidative burst (apocynin). Similar results were obtained when LTC4 synthase enzymatic activity was measured directly in the presence of saturating concentrations of exogenously added substrates. Therefore, the inhibitory effects of PKC activation on cysteinyl leukotriene formation in intact cells was attributable to effects on the LTC4 synthase enzyme. The mechanism of inhibition of LTC4 synthase by PKC activation was determined by kinetic analysis to be noncompetitive in both eosinophil-like HL-60#7 cells and monocytic THP-1 cells. Contrary to the effect of PKC activation on cysteinyl leukotriene biosynthesis, the formation of prostaglandin E2 and thromboxane B2 was elevated twofold to threefold after PMA treatment, which was prevented by the PKC inhibitor, staurosporine. We propose a regulatory model in which PKC activation shifts the profile of eicosanoid mediators produced by eosinophils from cysteinyl leukotrienes to prostanoids.
Dual regulation of cytosolic phospholipase A2 in mast cells after cross-linking of FC epsilon-receptor.
Authors: Nakatani Y , Murakami M , Kudo I , Inoue K 
Published: January 2023

Abstract
We have reported previously that cultured mast cells (MC) express three discrete phospholipases A2 (PLA2s), one of which corresponds to arachidonoyl-preferential cytosolic PLA2 (cPLA2). In the present study, we investigated the possible role of cPLA2 in eicosanoid synthesis by activating mouse bone marrow-derived mast cells (BMMC) through cross-linking of the high affinity IgE receptor (Fc epsilon RI) with a specific Ag. BMMC released arachidonic acid within 2 min after Fc epsilon RI cross-linking. A rapid, transient phosphorylation of cPLA2 was observed after Fc epsilon RI cross-linking, reaching the maximum within 2 min, and accompanied by an increase of cPLA2 activity in the cell lysate. Exposure of BMMC to the IgE-Ag for longer periods resulted in a time-dependent increase of the cPLA2 protein. The increase was detected within 10 h after stimulation and reached the maximum within 30 h. Dexamethasone inhibited the Ag-stimulated cPLA2 induction significantly. cPLA2 activity in cells stimulated for 24 h was increased significantly, and suppressed in cells treated with dexamethasone. When the cells were exposed to IgE-Ag for 36 h and then challenged with a secondary agonist, thrombin, arachidonate release was augmented significantly in comparison with cells without the Ag pretreatment. Thus, cPLA2 activation in BMMC by short term exposure to the Ag might be regulated by post-Fc epsilon RI modification (phosphorylation) of pre-existing enzyme, whereas that observed after long term exposure might be explained by the increase in cPLA2 protein.
Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides.
Authors: Vandenbark A A , Vainiene M , Celnik B , Hashim G A , Buenafe A , Offner H 
Published: January 2023

Abstract
Two distinct epitopes of guinea pig basic protein (Gp-BP), residues 72-89 and 87-99, possess encephalitogenic activity in Lewis rats. The purpose of this study was to determine to what degree the 87-99 epitope functions in rats that have been injected with whole Gp-BP, and whether additional epitopes in Gp-BP are encephalitogenic. To address these questions, we induced neonatal tolerance to the dominant synthetic (S)72-89 peptide or to the combination of both S72-89 and S87-99 peptides, and evaluated resistance to experimental autoimmune encephalomyelitis (EAE) induced by Gp-BP, as well as T cell responses to peptides that encompassed most of the Gp-BP molecule. The results demonstrated that virtually all of the encephalitogenic activity of Gp-BP resides within the two described encephalitogenic epitopes. Moreover, deletion of responses to the dominant epitopes prompted T cell responses to other nonencephalitogenic epitopes of Gp-BP, a pattern of response observed previously in rats that had recovered from EAE and in those protected from EAE by vaccination with TCR peptides. These data may have relevance to human autoimmune diseases such as multiple sclerosis in that naturally or immunologically regulated responses to dominant epitopes that are likely to be encephalitogenic may be obscured by increased responses to relatively innocuous determinants of basic protein. Elevated responses to potentially pathogenic autoantigens will likely involve both types of determinants, thus, underscoring the importance of distinguishing encephalitogenic from nonencephalitogenic determinants.
Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis rat. The utility of a class II binding motif in selecting self-reactive peptides.
Authors: Wegmann K W , Zhao W , Griffin A C , Hickey W F 
Published: January 2023

Abstract
Cardiac myosin (CM) has been implicated as an autoantigen in the induction of experimental allergic myocarditis (EAM). At the present time no myocarditogenic peptides of CM have been identified. To identify CM peptides with myocarditogenic properties we have made use of a putative binding motif for the MHC class II molecule RT1.BI in the rat. The amino acid sequence of CM alpha-chain was scanned and found to contain nine peptides that contain this binding motif, three peptides found only in the cardiac form of myosin were chosen for further study. This manuscript describes the identification of two CM peptides capable of inducing EAM in the Lewis rat. In doing so this study demonstrates the utility of an MHC class II binding motif to (correctly) predict pathogenic, autoimmunity inducing, peptides. Peptides, CM 1, and CM 2 are the first peptides described that are capable of inducing EAM in rats. The utilization of CM 2 peptide has permitted the establishment of a long term, Ag specific cell line capable of adoptively transferring EAM. Moreover, the establishment of CM 2 specific T lymphocyte lines has permitted the description of a detailed proliferative response of a myocarditogenic cell line to a specific cardiac Ag. The identification of CM 1 and 2 formally proves that CM, and not a co-purified contaminant, is an Ag in EAM. Finally, this report documents that experimentally induced giant cell myocarditis is not a separate disease entity arising from a distinct cardiac Ag or CM epitope from regular myocarditis.
Signaling via CD7 molecules on human NK cells. Induction of tyrosine phosphorylation and beta 1 integrin-mediated adhesion to fibronectin.
Authors: Rabinowich H , Lin W C , Herberman R B , Whiteside T L 
Published: January 2023

Abstract
We have previously reported that CD7 expressed on resting human NK cells is a signal-transducing molecule, which upon ligation with mAb induces a rapid increase in cytoplasmic free calcium, secretion of IFN-gamma, and augmented NK activity against K562 targets. We now demonstrate that Ab-mediated clustering of CD7 molecules on NK cells results in enhanced phosphorylation on tyrosine residues of intracellular proteins of 60, 70, 80, 97, and 120 kDa. In the presence of genistein, a specific inhibitor of protein tyrosine kinase, the enhanced level of tyrosine phosphorylation was blocked, indicating that CD7 may induce signaling via activation of tyrosine kinases. Cross-linking of CD7 or CD16 molecules with primary and secondary Abs, as well as stimulation of NK cells with phorbol ester (PMA) or with calcium ionophore A23187 also induced beta 1 integrin-mediated adhesion of these cells to fibronectin (FN)-coated plastic surfaces. In contrast, cross-linking of CD2 expressed on the surface of NK cells had no significant effect on NK cell adhesion to FN. This adhesion was not associated with up-regulation of expression of alpha 4 beta 1 or alpha 5 beta 1 FN receptors on NK cells, but it required an intact cytoskeleton. The CD7-induced adhesion to FN was mediated by alpha 4 beta 1 and alpha 5 beta 1 integrins, as it was partially blocked by FN connective segment-1 peptide (EILDVPST), the alpha 4 beta 1-binding domain, as well as by RGD-containing peptides, the alpha 5 beta 1-binding domain, but not by EILEVPST or RGE control peptides. NK cell binding to FN was also partially inhibited by mAb to alpha 4, alpha 5, and beta 1 integrins. The mechanism by which cross-linking of CD7 or CD16 on NK cells induced adhesion to FN appeared to involve both protein tyrosine kinase and protein kinase C, because this adhesion was blocked in the presence of either genistein or a protein kinase C inhibitor, staurosporin. Our data demonstrate that signals transduced via triggering of either CD7 or CD16 molecules are involved in the regulation of the functional activity of beta 1 integrins on NK cells.
Human IgE in SCID mice reconstituted with peripheral blood mononuclear cells from Dermatophagoides pteronyssinus-sensitive patients.
Authors: Pestel J , Jeannin P , Delneste Y , Dessaint J P , Cesbron J Y , Capron A , Tsicopoulos A , Tonnel A B 
Published: January 2023

Abstract
SCID mice were reconstituted with purified peripheral blood mononuclear cells from patients sensitive to Dermatophagoides pteronyssinus (Dpt). After immunization with a low dose of the related allergen, these human (Hu)-SCID mice may develop a specific IgE response. By using an IgE-dependent platelet assay and the related allergen Dpt, the human IgE was demonstrated to be functional. Indeed a high correlation was obtained between both parameters. No rise in human IgE level was detected within 3 wk after the immunization with an unrelated Ag. When mice were reconstituted with peripheral blood cells from nonallergic donors and immunized with the Dpt allergen, no human IgE production was evidenced in the serum of SCID mice. However, in both allergic Hu-SCID mice (reconstituted with cells from allergic patients) or in nonallergic Hu-SCID mice (reconstituted with cells from healthy donors), an IgG response was detectable. Finally by radioallergosorbent test, a specific IgE Ab response was detected after the first allergen challenge only in allergic Hu-SCID mice. Thus, without ethical constraints, SCID mice represent a useful model for analyzing the IgE response occurring in allergic patients.
Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease.
Authors: Krenger W , Snyder K M , Byon J C , Falzarano G , Ferrara J L 
Published: January 2023

Abstract
Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12--&gt;C57BL/6) or class I (bm1--&gt;C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4+ and CD8+ type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice.
Comparative studies of transcytosis and assembly of secretory IgA in Madin-Darby canine kidney cells expressing human polymeric Ig receptor.
Authors: Tamer C M , Lamm M E , Robinson J K , Piskurich J F , Kaetzel C S 
Published: January 2023

Abstract
Epithelial transport of polymeric IgA (pIgA) from its site of synthesis to the mucosal lumen is mediated by the polymeric Ig receptor (pIgR). During transcytosis, a disulfide bond forms between pIgR and pIgA, resulting in secretion of a covalently linked complex. To dissect further the intracellular processing and functions of pIgR, we have expressed the entire coding sequence of human pIgR cDNA in Madin-Darby canine kidney (MDCK) cells. Cloned transfected cells express human pIgR, as detected by immunofluorescence and by quantification of the cleaved extracellular domain of pIgR in culture supernatants. The function of transfected pIgR was confirmed by measuring vectorial transcytosis of 125I-labeled pIgA and its disulfide bonding to pIgR. Species specificity of transcytosis was determined by comparing transport of human, rat, and mouse pIgA in MDCK cells expressing either human or rabbit pIgR. pIgA from all three species was transported by both human and rabbit pIgR, with rat pIgA being transported to the greatest extent in each case. However, disulfide bonding was observed only with human pIgR, and was found to occur mainly inside the cell. Our results suggest that conformational differences between human and rabbit pIgR may account for differences in disulfide bonding to pIgA, and show that efficient transcytosis of pIgA is correlated better with noncovalent than covalent binding to pIgR.
Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression.
Authors: Chen Y , Inobe J , Weiner H L 
Published: January 2023

Abstract
We have previously shown that orally administered myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis in both the Lewis rat and the SJL mouse. In the Lewis rat fed low doses of MBP, we found that protection can be adoptively transferred by CD8+ cells and that these cells inhibit immune responses via the secretion of TGF-beta after Ag-specific triggering. In the present study, we investigated the cellular requirements for the generation of active suppression following oral administration of MBP in SJL and (PLJ x SJL)F1 mice. We first determined the frequency of MBP cells secreting Th1 (IFN-gamma) and Th2 (IL-4/IL-10) cytokines or TGF-beta after oral administration of MBP. We found that in SJL mice, orally administered MBP (0.5 mg/feeding) led to an increased frequency of TGF-beta-, IL-4-, and IL-10-secreting cells and a decreased frequency of IFN-gamma-producing cells. This pattern was observed in both CD4+ and CD8+ populations; adoptive transfer of either CD4+ or CD8+ cells from orally tolerized mice suppressed autoimmune encephalomyelitis in recipient animals. We then studied the role of CD8+ cells on the generation of oral tolerance to MBP by depleting CD8+ cells in vivo with anti-CD8 mAb. Oral tolerance was successfully induced in such animals, as demonstrated by a decrease in clinical disease and T cell proliferative responses, although there was less TGF-beta production in vitro and less disease protection on days 20 to 22 in CD8-depleted animals. These studies demonstrate that CD4+ cells in the absence of CD8+ cells can mediate the active suppression component of oral tolerance in mice and that there is a reciprocal relationship between Th1- and Th2-type cytokine production associated with oral tolerization.