bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective regional immunity in the respiratory tract of neonates is attributable to hyporesponsiveness of local dendritic cells to activation signals.
Authors: Nelson D J , Holt P G 
Published: December 2022

Abstract
A variety of studies suggest that the increased susceptibility of neonates to allergic and infectious respiratory diseases is due to delayed postnatal maturation of local mucosal immune function. We have recently demonstrated that the postnatal development of the major resident APC population in the respiratory tract (RT), class II MHC (Ia)-bearing dendritic cells (DC), is delayed relative to that in other tissues, and that both the intensity of Ia expression on these RTDC and their density within respiratory epithelia remain low until after weaning. The present study focuses on the functional capacity of neonatal RTDC and their responses to exogenous stimuli, and demonstrates that 1) infant Ia+ RTDC respond poorly to GM-CSF, under conditions that stimulate high levels of Ia expression and concomitant APC activity in adult cells; 2) both infant and adult RTDC contain a subpopulation of Ia- cells recognized by mAb OX62 that also respond poorly to GM-CSF; 3) inhalation of microbial stimuli or parenteral administration of IFN-gamma triggers rapid recruitment of DC into the airway epithelium and lung parenchyma of adults; this response is markedly attenuated in newborns and does not attain levels of competence until after weaning; and 4) endogenous macrophage-mediated suppression of the RTDC response to GM-CSF, the principal mechanism limiting in situ DC functional maturation in the adult lung, is highly active in the neonates. Taken together with earlier evidence of the relatively rapid postnatal development of T and B cell function in these animals, the present findings suggest that the sluggish performance of respiratory mucosal immune function(s) during infancy is attributable primarily to delayed maturation of local DC populations.
In vivo regulation of macrophage IL-12 production during type 1 and type 2 cytokine-mediated granuloma formation.
Authors: Chensue S W , Ruth J H , Warmington K , Lincoln P , Kunkel S L 
Published: December 2022

Abstract
IL-12 is a pivitol cytokine that promotes NK cell activity and Th1 (type 1)-mediated immune responses. This study analyzed the cytokines that regulate macrophage (M phi) IL-12 production in vitro and in vivo. IL-12 was produced by elicited but not resident peritoneal M phi stimulated with endotoxin. Addition of graded doses of cytokines (0.1 to 10 ng/ml) indicated that the Th1-related (type 1) cytokine, IFN-gamma, augmented endotoxin-stimulated IL-12 production by nearly sixfold in oil-elicited M phi. TNF-alpha also increased production but only at the 10 ng/ml concentration. In contrast, the Th2-related (type 2) cytokines, IL-4 and especially IL-10, were profoundly inhibitory. IL-1 beta and IL-2 had no effect. For in vivo analysis, type 1 and type 2 cytokine-mediated lung granulomas (GR) were induced in presensitized mice by embolization of beads coupled to purified protein derivative of Mycobacteria tuberculosis or soluble Ags derived from Schistosoma mansoni eggs. Analysis of M phi isolated from type 1, type 2, or control pulmonary GR revealed that M phi of type 2 GR develop impaired IL-12-producing capacity. Depletion studies using anti-IFN, anti-IL-12, anti-IL-10, and anti-IL-4 neutralizing polyclonal Abs corroborated the in vitro studies. Anti-IFN or anti-IL-12 reduced IL-12 production by M phi from type 1 GR (70 to 80%) as well as IFN and IL-12 production by draining lymph nodes (75 to 90%). Conversely, anti-IL-10 and anti-IL-4 reversed the impaired IL-12 production observed in type 2 GR M phi. These data indicate a positive feedback stimulation of IL-12 production by IFN that is regulated by IL-10 and IL-4 in vivo.
Characteristics of ATP-dependent peptide transport in isolated microsomes.
Authors: Yang B , Braciale T J 
Published: December 2022

Abstract
This report examines the transport properties and specificity of ATP-dependent peptide transport by the murine transporter for Ag presentation (TAP) complex in isolated microsome preparations from H-2d haplotype mice. The murine TAP complex has a Km of 661 nM and a maximum velocity of 2.9 fmol/min.micrograms microsome protein for a modified peptide corresponding to a defined MHC class I binding epitope from influenza nucleoprotein recognized by CD8+ CTL in association with the Kd molecule. This high Km value for peptide transport suggests that the rate and efficiency of peptide transport of the TAP complex are influenced by the concentration of processed peptides derived from self and foreign proteins in the cell cytoplasm. Furthermore, these findings imply that competition among peptides for TAP-dependent transport is unlikely to be an important factor in determining the immunodominance of certain peptide epitopes within a foreign protein recognized by CD8+ T lymphocytes. We also examined the specificity of TAP transport for peptides containing bona fide murine MHC class I binding epitopes and provide evidence that certain flanking residues can affect the efficiency of peptide epitope transport by the TAP complex.
Analysis of CD2 and TCR-beta gene expression in Jurkat cell mutants suggests a cis regulation of gene transcription.
Authors: Kamoun M , Woods J S , Sano N , Makni H , Smith R , de Lau W B , van Oers A , Wotton D , Owen M J , Hashimoto Y , Clevers H C 
Published: December 2022

Abstract
Thirty CD2- J32 stable clones, derived by mutagenesis and subsequent immunoselection with anti-CD2 Ab, were used to study the regulation of CD2 and TCR gene expression. Analysis of RNA expression revealed that the loss of surface expression of CD2 was due to a lack of expression of CD2 mRNA and was associated with a lack of expression of VDJ TCR-beta transcripts in 12 of these mutants, sparing the expression of DJ TCR-beta, TCR-alpha, CD3 gamma, delta, epsilon, and zeta RNA. The expression of other differentiation molecules was unaffected, except for CD1, CD4, and CD5, which were either decreased or absent in most of these mutants. A gain in the expression of TCR-gamma transcripts was observed in each of these mutants, while, as expected, no TCR-gamma transcripts were detected in wild-type J32 cells. Several mutants were able to use the human CD2 enhancer and the murine TCR-beta enhancer and promoter to activate transcription from reporter genes in the context of heterologous promoters, indicating that the mutation(s) does not affect transcription pathways. Consistent with this finding is the adequate expression in these mutants of several lineage-specific transcription factors. The expression of CD2 in several of these mutants was rescued by gene transfer using a genomic 28.5-kb CD2 fragment, suggesting that the enhancer function of this gene may be dependent on the enhancer site. These observations suggest that the coordinate expressions of CD2 and TCR-beta genes share common regulatory mechanisms involving factors regulating chromatin structure and accessibility.
Cytokine and nitric oxide regulation of the immunosuppression in Trypanosoma cruzi infection.
Authors: Abrahamsohn I A , Coffman R L 
Published: December 2022

Abstract
An intense suppression of splenic T cell proliferation to mitogens and to Ags from the parasite is characteristic of the acute phase of Trypanosoma cruzi infection in mice. The impairment of proliferation is coincident with high levels of IFN-gamma and nitrite and decreased production of IL-2 in the supernatants of spleen cell cultures from infected mice. Previous work demonstrated that suppression of proliferation is largely mediated by the population of adherent cells in the infected spleen. In this study we confirmed the active suppression exerted by these cells on Con A, anti-CD3, and parasite Ag-stimulated proliferation of CD4+ splenic T cells. Inasmuch as the high production of IFN-gamma and of nitrite were compatible with intense macrophage activation and nitric oxide (NO) production, we determined the effects of cytokines that regulate macrophage activation and of NO on the proliferation of spleen cells from infected mice. We show that spleen cell proliferation to Ag and to T cell polyclonal stimuli is increased by neutralizing mAbs to IFN-gamma, TNF-alpha and -beta, or by the inhibitor of NO synthase, NG-monomethyl-L-arginine, added to the cultures. The addition of rIL-2 or rIL-4 also contributed to suppression reversal, and the combined addition of rIL-2 and anti-IFN-gamma mAb further increased lymphocyte proliferation. Anti-IL-4, anti-IL-10, or anti-TGF-beta neutralizing mAbs did not modify suppressed proliferative responses, and the addition of rIL-10 or of rTGF-beta also did not recover cell proliferation. Thus, the suppression of proliferative responses in T. cruzi-infected mice resulted largely from increased NO production by macrophages activated by IFN-gamma and TNF allied to insufficient IL-2 to fully support in vitro growth of T lymphocytes.
Differential responsiveness of purified mouse c-kit+ mast cells and their progenitors to IL-3 and stem cell factor.
Authors: Lantz C S , Huff T F 
Published: December 2022

Abstract
Murine mast cell development is regulated by a number of T cell- and fibroblast-derived growth factors, of which IL-3 and stem cell factor (SCF) appear to be the most important. To determine the relative effects of these two growth factors on different stages of developing mast cells, we isolated highly purified populations of c-kit+ mast cells and their progenitors and examined their ability to respond to SCF and/or IL-3. We show that purified c-kit+ cells isolated from bone marrow, mesenteric lymph nodes of Nippostrongylus brasiliensis-infected mice, and the peritoneal cavity do not form mast cell colonies in response to SCF as a single agent. Although unpurified populations of lymph nodes of Nippostrongylus brasiliensis-infected mice or peritoneal cells were able to form mast cell colonies in response to SCF alone, this probably reflects paracrine factors produced by accessory cells. IL-3 alone did not promote mast cell colony formation from either population. Within bone marrow, we detected both multipotential and unipotential mast cell progenitors. Interestingly, IL-3 alone promoted only the development of multipotential progenitors, while SCF plus IL-3 promoted both multipotential and unipotential mast cell progenitors. Together, these results indicate that the developmental/proliferative effects observed with a particular mast cell population is determined in part by the stage of maturation of mast cells at the time they are exposed to SCF and IL-3, and suggest that SCF primarily influences mast cell development only in the context of other cytokines.
Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease.
Authors: Cua D J , Hinton D R , Stohlman S A 
Published: December 2022

Abstract
Immunization of a limited number of rodent strains with central nervous system-derived Ags induces experimental allergic encephalomyelitis (EAE). In contrast to susceptible female SJL mice, age-matched males are resistant to actively induced EAE. The ability of immunization with neuroAg to induce Ag-specific T cell activation in resistant male mice was examined. Ag-specific T cell proliferation was found following immunization of both male and female SJL mice. Draining lymph node cytokine mRNA patterns demonstrated that immunization of EAE-resistant male mice resulted in a Th2-type pattern. By contrast, immunization of EAE-susceptible female mice resulted in a Th1-type pattern. Priming of Th1- and Th2-type responses was confirmed by analysis of cytokines secreted following Ag-specific proliferation. In contrast to the transfer of myelin basic protein (MBP)-specific Th1-type T cells derived from female mice, which induced acute and relapse EAE, transfer of MBP-specific Th2-type T cells derived from male mice resulted in no clinical or histologic evidence of EAE. A mixture of MBP-specific Th1 and Th2 type cells was transferred to naive recipients to determine if the neuroAg-specific Th2-type cells exerted a regulatory influence on EAE. Acute disease was partially eliminated and relapses were completely eliminated in these recipients. Analysis of spinal cords showed the presence of both Th1 and Th2 cytokine mRNAs. These data are consistent with both the ability of Th2-type cells to suppress autoimmunity and a homeostatic mechanism of T cell regulation based on the cross-regulation of Th1 and Th2 cells in the maintenance of peripheral tolerance.
Relationship between beta cell injury and antigen presentation in NOD mice.
Authors: Shimizu J , Carrasco-Marin E , Kanagawa O , Unanue E R 
Published: December 2022

Abstract
We have made three observations that are important for our understanding of the dynamics of presentation of diabetogenic Ags in immunologically induced diabetes. First, the APC in the islets of Langerhans were found normally to contain diabetogenic peptides on their I-Ag7 molecules. This was found in freshly harvested islet cells from prediabetic NOD mice and, importantly, from NOD.SCID mice. Second, the presence of diabetogenic lymphocytes improved the presenting function of intra-islet APC. We interpret this to mean that lymphocytes can regulate intra-islet APC function before the development of diabetes. Finally, spleen APC can be found bearing diabetogenic Ag after acute injury to islets. These APC may be important in lymphocyte stimulation outside the environment of the pancreas.
High avidity state of leukocyte function-associated antigen-1 on rheumatoid synovial fluid T lymphocytes.
Authors: Yokota A , Murata N , Saiki O , Shimizu M , Springer T A , Kishimoto T 
Published: December 2022

Abstract
The integrin LFA-1 (CD11a/CD18) is a cell surface adhesion molecule required for leukocyte extravasation and subsequent immune and inflammatory responses. Rapid transition between nonadherent and adherent states of LFA-1 is of key importance to Ag-specific recognition of T lymphocytes. In this paper, LFA-1-mediated adhesiveness of peripheral blood (PB) and synovial fluid (SF) T lymphocytes to affinity-purified ICAM-1-coated plates was studied in patients with rheumatoid arthritis (RA) and in patients with non-RA panels, including osteoarthritis, ankylosing spondylitis, erythema nodosum, pseudogout, and pustulosis. LFA-1-mediated adhesiveness of SF T lymphocytes was not observed in any of the 10 non-RA patients studied, although cross-linking of the TCR on lymphocytes from these patients rapidly converted LFA-1 to an adhesive state. In contrast, SF T lymphocytes from 10 of 12 RA patients exhibited LFA-1-mediated adhesiveness without a requirement for cross-linking of the TCR. No difference was seen in the cell surface density of LFA-1 between non-RA and RA T lymphocytes, suggesting that the difference in adhesiveness was due to a high avidity state of LFA-1 on SF T lymphocytes in RA. Furthermore, exposure of PB T lymphocytes, which showed a low avidity state of LFA-1, to whole SF from RA patients that was depleted of T lymphocytes could induce a high avidity state of LFA-1 in vitro. Cellfree SF from RA patients also could stimulate adhesiveness, although to a lesser extent. These data suggest the existence of a LFA-1-activating environment that is selectively found in SF from RA patients.
Identification of epitopes within a highly immunogenic region of acetylcholine receptor by a phage epitope library.
Authors: Barchan D , Balass M , Souroujon M C , Katchalski-Katzir E , Fuchs S 
Published: December 2022

Abstract
We have employed a hexapeptide phage-epitope library to identify epitopes for a mAb (mAb 5.14), which is directed to a determinant within a highly immunogenic, cytoplasmic region of the alpha-subunit of acetylcholine receptor (AChR). We have selected two different peptide-presenting phages (SWDDIR-phage and LWILTR-phage) which interact specifically with mAb 5.14. This interaction is specifically inhibited by AChR and by synthetic peptides corresponding to the hexapeptides presented by the selected phages. Although mAb 5.14 binds to AChR in its native as well as its denatured form, the selected hexapeptides do not exist as such in the AChR molecule. However, three amino acid sequence homologies with these hexapeptides were shown to be present in the cytoplasmic region of Torpedo AChR. By extending the selected hexapeptides, at one or both ends, with amino acid residues flanking the hexapeptides in the phage, we obtained mimotopes with an up to two order of magnitude higher affinity to the Ab. These extended peptides were able to efficiently block the binding of mAb 5.14 to both peptide-presenting phages, and to AChR.
IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase-2.
Authors: Murakami M , Bingham C O , Matsumoto R , Austen K F , Arm J P 
Published: December 2022

Abstract
Mouse bone marrow-derived mast cells (BMMC) developed with IL-3 generate prostaglandin D2 (PGD2) through the utilization of prostaglandin endoperoxide synthase (PGHS)-1 within several minutes of cross-linking the high affinity Fc receptor for IgE (Fc epsilon RI) by hapten-specific IgE and Ag. We now report that this immediate generation of PGD2 is followed by a 15-fold induction of steady-state transcripts for PGHS-2, with a maximum at 30 min, accompanied by transient expression of PGHS-2 protein. When BMMC were pretreated with c-kit ligand (KL) in combination with IL-10 for 2 h, sensitized with IgE, and activated with Ag, their expression of steady-state transcripts for PGHS-2 increased 111-fold and their expression of PGHS-2 protein was markedly enhanced, with maximal expression at 1 h and 5 h, respectively, after activation. These events were accompanied by PGD2 generation from 1 to 10 h after activation that accounted for approximately 50% of total PGD2 generation. The expression of PGHS-1 protein did not change during this period. The optimal priming interval for the effect of KL plus IL-10 on the IgE-dependent induction of PGHS-2 was 2 h, at which time only this particular cytokine combination acted synergistically with activation by IgE and Ag. In contrast, at 2 days the accessory cytokines that could provide priming with KL included IL-3 and IL-9 in addition to IL-10. Dexamethasone, which inhibited the expression of PGHS-2 but not PGHS-1, and NS-398, a selective inhibitor of PGHS-2, each suppressed the delayed phase but not the immediate phase of PGD2 generation. Conversely, valeryl salicylate, a selective inhibitor of PGHS-1, suppressed the immediate but not the delayed phase of PGD2 generation after cell priming and IgE-dependent activation.
Staphylococcal enterotoxin D functions as a human B cell superantigen by rescuing VH4-expressing B cells from apoptosis.
Authors: Domiati-Saad R , Attrep J F , Brezinschek H P , Cherrie A H , Karp D R , Lipsky P E 
Published: December 2022

Abstract
Staphylococcal enterotoxins are potent superantigens, in that they activate T cells bearing specific V beta-chain gene segments. In this study, we analyzed the capacity of staphylococcal enterotoxin D (SED) to function as a B cell superantigen. SED induced T cell-dependent polyclonal proliferation and differentiation of B cells. In the absence of T cells, SED induced survival of B cells uniquely expressing VH4 containing IgM. The mechanism of survival of VH4-expressing B cells appeared to relate to the countering of apoptosis initiated by the engagement of HLA-DR by SED. Analysis of the VH4 gene products expressed by SED-stimulated B cells revealed the usage of six of the known functional VH4 genes with a variety of different CDR3 regions, employing different DH and JH gene segments. Moreover, the sequence analysis identified a possible site for SED binding of VH4 that includes the solvent-exposed surfaces of 3' CDR2/FR3 and/or FR1. Thus, SED appears to function as a unique B cell superantigen by inducing survival of VH4-expressing B cells.
Aberrant regulation of cytokines in HIV-1 TAT72-transgenic mice.
Authors: Garza H H , Prakash O , Carr D J 
Published: December 2022

Abstract
The trans-activator of transcription or TAT gene from HIV-1 encodes a protein that increases the processivity of transcription from the HIV-1 genome. TAT protein can also affect cellular processes in the absence of its ribonucleic HIV target sequence trans activation response element and may be responsible for some aspects of HIV pathogenesis apart from infectious virus or other viral gene products. We have previously shown that TAT72 decreases CTL activity in TAT72-transgenic mice, and we now demonstrate aberrant regulation of mitogen-elicited IL-2 at both transcriptional and translational levels. In contrast, alloantigen stimulation resulted in increased IL-6 and IL-10 production in the TAT72-transgenic mice. Con A-stimulated cultures of splenic lymphocytes from TAT72-transgenic mice do not undergo clonal proliferation of CD4+ cells as compared with CD8+ cells monitored over 72 h. These results suggest that TAT is sufficient to induce some pathology associated with AIDS and is a potent immunologic manipulator apart from its function as trans-activator.
Generation of a new gamma delta T cell-specific monoclonal antibody (GD3.5). Biochemical comparisons of GD3.5 antigen with the previously described Workshop Cluster 1 (WC1) family.
Authors: Jones W M , Walcheck B , Jutila M A 
Published: December 2022

Abstract
In this report, we describe GD3.5, a new lineage-specific gamma delta T cell marker that is distinct from TCR and known Workshop Cluster 1 (WC1). FACS analysis indicated that GD3.5Ag is expressed on approximately 90% of the peripheral blood gamma delta T cell population and GD3.5 specifically stained gamma delta T cells and not alpha beta T cells, B cells, neutrophils, or monocytes. Also, a significant portion of the GD3.5-positive population was WC1-negative. Nonreducing Western blot analysis and immunoprecipitation experiments revealed a single 220- to 240-kDa glycoprotein recognized by GD3.5 compared with two WC1 bands at 200 kDa and 300 kDa recognized by the IL-A29 Ab. Cross-immunoprecipitation experiments demonstrated that GD3.5 could be immunoprecipitated from lysates cleared of IL-A29/WC1 complexes. Reciprocally, WC1 could be immunoprecipitated from lysates cleared of GD3.5Ab/GD3.5Ag complexes. Digestion of WC1 and GD3.5 Ag with V-8 protease resulted in digestion profiles that clearly distinguished the glycoproteins. Additionally, GD3.5 Ag and WC1 possess disparate sensitivity to PNGase F, O-sialoglycoprotease, and neuraminidase, indicating differences in N- and O-linked sugars and the presence of sialic acid residues. Both GD3.5 Ag and WC1 appeared to be sialomucin-like molecules that share similar O-sialoglycoprotein endopeptidase sensitivity with other cell surface molecules, such as PSGL-1. Lastly, GD3.5 Ag, but not WC1, was exquisitely sensitive to very low-dose chymotrypsin treatment. Therefore, our data suggest that GD3.5 Ag is a previously uncharacterized, lineage-specific gamma delta T cell Ag. Furthermore, we show that GD3.5 and WC1 are sialomucins, which provides important clues to their function.