bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circumvention of defective CD4 T helper cell function in HIV-infected individuals by stimulation with HLA alloantigens.
Authors: Clerici M , Stocks N I , Zajac R A , Boswell R N , Via C S , Shearer G M 
Published: January 2023

Abstract
PBL from approximately 50% of asymptomatic individuals infected with HIV have been previously demonstrated to exhibit defective in vitro Th function that is selective for influenza A virus (FLU), but not for HLA alloantigens (ALLO). In this report, we have further studied HIV+ individuals with this selective Th defect, and demonstrate that defective in vitro CTL responses to FLU can be restored by costimulation with FLU + ALLO. In contrast, HIV+ patients who have lost Th responses to ALLO were unable to correct CTL responses to FLU by this costimulation procedure. These findings indicate that intact Th responses to ALLO can be used in vitro to provide Th signals necessary to activate the T effector cell response to a potential pathogenic virus. Our results raise the possibility that a program of in vivo coimmunization with ALLO plus antigens of potential pathogens (including HIV) can be useful in HIV+ patients exhibiting selective defects in Th function. Furthermore, this approach could be incorporated in vaccine trials aimed at enhancing immunity to HIV in patients who have been infected previously with this virus.
Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells.
Authors: Lee W T , Yin X M , Vitetta E S 
Published: January 2023

Abstract
CD4+ murine T cell clones, TH1 and TH2, can be distinguished by both functional responses and by their patterns of lymphokine secretion. Recently, a mAb, 23G2, which reacts with a subset of CD45 molecules (CD45R), has been reported to bind differentially to clones of TH1 and TH2 cells. In the present study, normal splenic T cells were analyzed for differences in 23G2-reactivity and were separated into two populations based on their density of CD45R (CD45Rhi and CD45Rlo). The CD45Rhi cells secrete more IL-2 than IL-4 after stimulation in vitro; the reverse is true for the CD45Rlo cells. Because neither population secretes only IL-2 or IL-4, we were unable to classify cells as TH1 or TH2. In vivo and in vitro analyses of the CD45Rhi and CD45Rlo cells suggest a lineage relationship between the two subsets that correlates with the degree of Ag exposure and the state of maturation of the mice. In newborn mice and mice raised under sterile conditions, splenic CD4+ T cells are predominantly CD45Rhi. Under conditions of increased antigenic exposure and maturation of the mice, CD45Rlo cells develop; after long term priming in vivo, the majority of specific Ag-reactive cells are CD45Rlo. Adoptive transfer studies using BALB/c nu/nu recipients demonstrate that CD45Rhi cells become CD45Rlo cells and that the recall response (IgG) to specific Ag is mediated by CD45Rlo cells. Taken together, these data indicate that the level of expression of CD45R on CD4+ T cells distinguishes virgin (CD45Rhi) from primed/memory (CD45Rlo) T cells in normal mice.
An absence of T cells in murine bone marrow allografts leads to an increased susceptibility to rejection by natural killer cells and T cells.
Authors: Murphy W J , Kumar V , Cope J C , Bennett M 
Published: January 2023

Abstract
The mechanisms behind the increased incidence of marrow graft failure in recipients that receive allogeneic marrow depleted of T cells were studied. Recipient mice were lethally irradiated and challenged with bone marrow cells (BMC) from C.B-17 +/+ (+/+) donors. Radioisotope 125IUdR incorporation was assessed 5 to 7 days after transfer to determine the extent of engraftment. Some groups received BMC in which the T cells were removed by treatment with antibody and C. In addition, some groups received BMC from T cell-deficient C.B-17 scid/scid (SCID) mice to determine the postulated need for donor T cells in hematopoiesis and engraftment. In a model system that distinguishes between possible host NK cell and radioresistant T cell-mediated rejection of marrow allografts, it was determined that the absence of donor T cells in a marrow graft does not affect engraftment in syngeneic recipients. However, both host NK cell and radioresistant T cell rejection was markedly enhanced when SCID BMC or BMC from C.B-17 +/+ donors that had T cells removed by antibody and complement were infused into irradiated allogeneic recipients. Furthermore, the addition of alloreactive thymocytes as a source of T cells could abrogate this increased susceptibility of the BMC to host rejection mechanisms. As determined by histology and 59Fe uptake, the addition of thymocytes resulted in enhanced erythropoiesis. These results suggest that the increased incidence of marrow graft failure when BMC depleted of T cells are used is a result of active rejection by host effector cells and that the adverse effect of marrow T cell depletion can be reversed by the addition of thymocytes.
IL-4 blocks the up-regulation of IL-2 receptors induced by IL-2 in normal human B cells.
Authors: Lee H K , Xia X , Choi Y S 
Published: January 2023

Abstract
A negative influence of IL-4 on the IL-2-induced B cell proliferation and differentiation has recently been reported. In this study, we have further investigated a role of IL-4 on human tonsillar B cell proliferation and IL-2R expression. IL-4 enhanced Staphylococcus aureus Cowan 1 strain (SAC)-induced B cell proliferation, reaching the peak on day 3. However, from day 4, IL-4 inhibited IL-2-induced proliferation. In the cross-linking study, IL-4 enhanced the density of 125I-IL-2-binding protein at low affinity binding condition (2 nM of 125I-IL-2) in SAC-activated B cells. However, IL-4 blocked the enhancement in the density of 125I-IL-2-binding proteins induced by IL-2, from day 3, in both high (50 pM of 125I-IL-2) and low affinity binding conditions, suggesting that IL-4 is able to block IL-2-induced IL-2R up-regulation. This was confirmed by a binding study: B cells that cultured for 3 days with SAC plus IL-2 expressed an average of 180 +/- 20 high affinity receptors/cell with a Kd of 12 pM and 5800 +/- 500 low affinity receptors/cell with a Kd of 980 pM. By coculturing with IL-4, high affinity receptors were almost undetectable and the expression of low affinity receptors was reduced by more than 80%. IL-4-mediated inhibition of IL-2-induced IL-2R expression does not seem to be due to the direct interaction between IL-4 and cell surface receptors, inasmuch as preincubation of cells with IL-4 for 60 min at 37 degrees C did not alter the binding of 125I-IL-2 to cells previously cultured for 3 days with SAC plus IL-2. These data suggest that IL-4 has a capacity to block the up-regulation of the high as well as low affinity IL-2R-induced by IL-2 in normal human B cells, and could provide a possible explanation for the decreased responsiveness of B cells to IL-2 in the presence of IL-4.
On the mechanism of action of dexamethasone in a rat mast cell line (RBL-2H3 cells). Evidence for altered coupling of receptors and G-proteins.
Authors: Collado-Escobar D , Ali H , Beaven M A 
Published: January 2023

Abstract
Prolonged exposure of rat basophilic leukemia (RBL-2H3) cells, a cultured analog of rat mast cells, to 0.1 microM dexamethasone resulted in global suppression of various stimulatory events in response to Ag and a global enhancement of the same stimulatory events to the adenosine analog, N-(ethylcarboxamide)adenosine (NECA). We had previously shown that Ag and NECA both activate phospholipase C but by different mechanisms; cells that had been treated with cholera or pertussis toxin, for example, responded to Ag but not to NECA with the release of inositol phosphates, increase in levels of cytosolic Ca2+, and secretion. Because the toxins still inhibited the responses to NECA in dexamethasone-treated cells, the effects of dexamethasone may have been exerted at the level of receptor/G-protein coupling rather than at the level of effector systems. Additional evidence for this was the following: 1) NECA-induced hydrolysis of the inositol phospholipids was still enhanced after permeabilizing (with streptolysin O or Staphylococcus alpha-toxin) and washing the cells; 2) the response to the G-protein stimulant, guanosine 5'-(3-O-thio)triphosphate was also enhanced in permeabilized, dexamethasone-treated cells and 3) binding and kinetic studies suggested that the enhanced responsiveness to NECA was attributable in part to an increase in receptor number. The suppressive action of dexamethasone on Ag-induced hydrolysis of inositol phospholipids, however, was readily lost by permeabilizing RBL-2H3 cells. The results indicate, therefore, that treatment with dexamethasone leads to changes in receptor-coupling mechanisms that are either resistant to (i.e., NECA-mediated responses) or reversed by (i.e., Ag-mediated responses) cell permeabilization.
Importance of subtype in the immune response to the pre-S(2) region of the hepatitis B surface antigen. I. T cell fine specificity.
Authors: Milich D R , Hughes J L , McLachlan A , Langley K E , Thornton G B , Jones J E 
Published: January 2023

Abstract
Previous studies of murine T cell recognition of the pre-S(2) region of the hepatitis B surface Ag (HBsAg) identified high (H-2b,d,q), intermediate (H-2s,k), and low to nonresponder (H-2f) haplotypes. However, these studies utilized the y subtype of HBsAg. The purpose of this study was to examine the influence of viral subtype on T cell recognition of the pre-S(2) region and to identify specific T cell recognition sites in a panel of H-2 congenic strains. Immunization with pre-S(2) containing HBsAg particles of the d and y subtypes indicated that T cell recognition of the pre-S(2) region is predominantly subtype-specific in murine strains of eight different H-2 haplotypes. Furthermore, the B10.M strain (H-2f) classified as a T cell nonresponder to the y subtype of the pre-S(2) region responds efficiently to the d subtype, indicating that pre-S(2) responder status can be subtype-dependent as well as subtype-specific. Studies using a truncated pre-S(2) polypeptide and synthetic peptides illustrated that the C-terminal sequence (p148-174) of the pre-S(2) region is the dominant focus of T cell recognition in multiple murine strains. Specifically, 17 distinct T cell recognition sites were defined within the C-terminal half of the pre-S(2) region. The fine specificity of T cell recognition of the pre-S(2) region was dependent on the H-2 haplotype of the responding strain. T cell recognition of all 17 sites was subtype specific, which is consistent with the fact that the C-terminal sequence is highly polymorphic between the d and y subtypes of the pre-S(2) region. Lastly, it was shown that the ability of synthetic peptides to elicit T cells cross-reactive with the native pre-S(2) region was variable and depended on the nature of the immunizing peptide. The pre-S(2)-containing HBsAg vaccines currently in clinical trials are composed of ra single subtype, either d or y. The results of this study suggest that both subtypes should be incorporated to increase the frequency of T cell responders to the pre-S(2) region, and to insure Th cell memory relevant to infection with hepatitis B virus of either the d or y subtypes.
Expression of IgE from a nonrearranged epsilon locus in cloned B-lymphoblastoid cells that also express IgM.
Authors: Chan M A , Benedict S H , Dosch H M , Hui M F , Stein L D 
Published: January 2023

Abstract
During development, B lymphocytes have the ability to switch from synthesis of IgM to immunoglobulins of another isotype such as IgG, IgA, or IgE. This class switching mechanism has been shown to involve DNA rearrangement and concomitant deletion of intervening CH genes. In our report, an EBV-transformed B lymphoblastoid cloned cell line is described that simultaneously expressed and secreted both IgM and IgE. DNA analysis showed the (nonproductive) rearrangement of one allele to gamma and (productive) rearrangement of the other allele to mu. Germ-line arrangement of the C epsilon gene was preserved on both alleles.
Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines.
Authors: Nuñez G , London L , Hockenbery D , Alexander M , McKearn J P , Korsmeyer S J 
Published: January 2023

Abstract
The t(14;18) of human follicular B cell lymphoma translocates the Bcl-2 gene into the Ig H chain locus and markedly deregulates Bcl-2 expression. We sought to determine if Bcl-2 could be directly implicated in a growth-factor pathway. Consequently, we introduced a retrovirus containing the murine Bcl-2 gene (N2-M-Bcl-2) or the parental retrovirus (N2) into a series of factor-dependent hemopoietic cell lines. Overexpressed Bcl-2 resulted in no long term IL-2, IL-3, or IL-6 independent clones, indicating that Bcl-2 could not spare the need for a specific ligand-receptor interaction. However, Bcl-2 did extend the short term survival of IL-3-dependent cell lines after factor deprivation. Although viable, IL-3-deprived pro B lymphocytes (FL5.12) bearing N2-M-Bcl-2 were in Go, and deregulated Bcl-2 did not obviously influence cell-cycle progression. Bcl-2 predominant effects were to delay the onset of cell death and to modestly augment viable cell growth in the first 48 h after IL-3 deprivation. This death sparing was associated with increased levels of Bcl-2 RNA and protein in factor-deprived cells possessing N2-M-Bcl-2. This result was not restricted to prolymphocytes because an IL-3-dependent mast cell line (32D) as well as a promyeloid line (FDC-P1) demonstrated the same response to Bcl-2. Moreover, the effect was not limited to the IL-3/IL-3R signal transduction pathway in that promyeloid cells maintained in granulocyte-macrophage-CSF or IL-4 displayed a similar response. Yet, Bcl-2-enhanced cell survival was not universal as an IL-2-dependent T cell line, and an IL-6-dependent myeloma line demonstrated no consistent effect upon IL withdrawal. Thus, Bcl-2 appears to interfere with cell death but in a cell type and/or factor-restricted fashion.
Hybridomas derived from lipopolysaccharide-activated anti-mu-treated B cells have active suppression of IgM secretion, demonstrable by secondary fusion.
Authors: Lawton A R , Summerlin V S , Dooley J S 
Published: January 2023

Abstract
Treatment of LPS-stimulated mouse B cells with bivalent anti-mu antibodies suppresses differentiation to Ig-secreting cells without interfering with proliferation. This treatment selectively inhibits up-regulation of transcription of differentiation-related genes. Induction of anti-mu suppression requires RNA and protein synthesis, suggesting involvement of a transcriptional repressor. We describe experiments designed to capture the repressed phenotype of anti-mu-treated cells. Fusions of anti-mu-treated cells with the B lymphoma line M12.4.5, but not plasmacytoma Ag8.653, yielded a significantly lower frequency of secretory hybridomas than did parallel fusion of cells treated with LPS only. To test for active repression, nonsecreting cloned hybridomas were secondarily fused to LPS-activated normal B cells. Secondary hybridomas with anti-mu parentage had a very low frequency of IgM secretion. Active suppression could only be demonstrated by secondary fusion. Neither supernatants nor extracts of repressor hybridomas influenced LPS-driven differentiation of normal B cells. These results confirm that this form of differentiation suppression is an active process, probably mediated by transcriptional controls. Repressor hybridomas should prove useful for studies of molecular mechanisms.
Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice.
Authors: Donnelly R P , Levine J , Hartwell D Q , Frendl G , Fenton M J , Beller D I 
Published: January 2023

Abstract
IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down-regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways.
Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies.
Authors: Tyler D S , Stanley S D , Zolla-Pazner S , Gorny M K , Shadduck P P , Langlois A J , Matthews T J , Bolognesi D P , Palker T J , Weinhold K J 
Published: January 2023

Abstract
In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.
cAMP differentially regulates expression of mRNA encoding IL-1 alpha and IL-1 beta in murine peritoneal macrophages.
Authors: Ohmori Y , Strassman G , Hamilton T A 
Published: January 2023

Abstract
The influence of PGE2 and the consequent rise in intracellular cAMP on LPS-induced IL-1 alpha and IL-1 beta mRNA levels has been examined in murine peritoneal macrophages. As has been previously reported, neither PGE2 nor dibutyryl cAMP modulated the levels of LPS-induced IL-1 alpha mRNA. In contrast, the levels of IL-1 beta mRNA were markedly potentiated (greater than 10 fold) under the same experimental conditions. This effect was due to elevation of intracellular cAMP because other agents known to elevate cAMP levels (e.g., cholera toxin, forskolin, 1-isomethyl-3-isobutylxanthine) had the same selective effect on IL-1 beta mRNA levels. PGE2 and dBcAMP not only potentiated LPS-induced IL-1 beta mRNA levels but were also able to stimulate modest accumulation of IL-1 beta mRNA in the absence of LPS. Although measurement of IL-1 activity by bioassay suggested that dBcAMP and PGE2 could suppress LPS-induced IL-1 expression, levels of IL-1 protein, determined by radioreceptor assay, were markedly elevated. cAMP did not appreciably alter the stability of either IL-1 alpha or IL-1 beta mRNA. Instead dBcAMP independently stimulated the transcriptional activity of the IL-1 beta gene. In concert the results demonstrate that cAMP can modulate the response of mononuclear phagocytes to LPS in a complex pattern; gene expression may be unaltered, suppressed, or potentiated and will thereby affect both the quality and magnitude of the ensuing inflammatory response.
A small proportion of cationic antibodies in immune complexes is sufficient to mediate their deposition in glomeruli.
Authors: Gauthier V J , Mannik M 
Published: January 2023

Abstract
Positively charged antibodies mediate enhanced deposition of circulating immune complexes at the glomerular basement membrane. The presented experiments demonstrate that when soluble immune complexes were prepared with a mixture of antibodies containing 10 to 25% cationic antibodies, then noncationic antibodies in the complexes were deposited in mouse glomeruli. One or two cationic antibodies in each immune complex sufficed for deposition of the complexes. Proof for this was obtained by two kinds of experiments. First, the injected immune complexes were prepared in Ag excess from mixtures of radiolabeled noncationic rabbit antibodies to human serum albumin (HSA) and unlabeled cationized rabbit antibodies to HSA, thus permitting the specific quantitation of the deposition of noncationic antibodies in glomeruli because of the presence of cationized antibodies within the same complexes. As a control experiment, immune complexes prepared only with noncationic antibodies resulted in very little deposition in kidneys over the same time period. Second, detection of the localization of the noncationic antibody in deposits in glomeruli by immunofluorescence microscopy was accomplished using immune complexes prepared with mixtures of noncationic goat antibodies to HSA and cationized rabbit antibodies to HSA. Thus, the synthesis of a small population of cationic antibodies during the immune response may lead to the formation of circulating immune complexes with enhanced propensity for deposition in glomeruli in patients with SLE or other immune complex diseases.