bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cDNA clone encoding the mouse Qa-1a histocompatibility antigen and proposed structure of the putative peptide binding site.
Authors: Connolly D J , Cotterill L A , Hederer R A , Thorpe C J , Travers P J , McVey J H , Dyson J , Robinson P J 
Published: January 2023

Abstract
We have isolated a cDNA clone which encodes the Qa-1a histocompatibility Ag from a library prepared from Con A-activated B10.BR mouse spleen cells. The clone encodes a protein of 322 amino acids with three potential N-glycosylation sites. The coding sequence shows strongest similarity with that of the T23d gene of DBA/2 mice which encodes the Qa-1b molecule. Molecular modeling of the putative peptide-combining site indicates most of the differences between Qa-1a and Qa-1b are located peripheral to the binding cleft, with only two amino acid substitutions, at positions 9 and 24, which might affect peptide binding. Many features of the Qa-1 binding cleft are also conserved in the rat RTBM.1 and in human HLA-E molecules. This suggests that all of these molecules may associate with structurally similar peptides.
Beta 2M-/- knockout mice contain low levels of CD8+ cytotoxic T lymphocyte that mediate specific tumor rejection.
Authors: Lamousé-Smith E , Clements V K , Ostrand-Rosenberg S 
Published: January 2023

Abstract
C57BL/6 mice with a disrupted beta 2M gene (beta 2M-/- mice) express very low levels of MHC class I molecules and are deficient for CD8+ T lymphocytes. Because CD8+ T cells are thought to be a principle effector cell in tumor rejection, we have assessed the ability of beta 2M-/- mice to respond to tumors. beta 2M-/- knockout mice were challenged with seven independent MHC allogeneic and syngeneic tumors. The beta 2M-/- mice responded very similarly to their CD8+ beta 2M+/- littermates in that they rejected high dose challenges of 4/5 allogeneic tumors and were susceptible to 3/3 syngeneic tumors. In vivo depletion of CD4+ or CD8+ cells from the beta 2M-/- mice resulted in susceptibility to allogeneic tumor. The apparent requirement for CD8+ cells for tumor immunity was corroborated by in vitro assays in which depletion of CD8+ but not CD4+ T cells eliminated tumor-specific CTL activity. mAb blocking studies in which target tumor cells were incubated with MHC class I-specific mAb demonstrated that the tumor-specific CD8+ activity was MHC class I restricted. beta 2M-/- mice therefore contain very small quantities of potent, CD8+ T cells that are capable of rejecting large challenges of allogeneic tumor cells.
Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10.
Authors: de Waal Malefyt R , Figdor C G , Huijbens R , Mohan-Peterson S , Bennett B , Culpepper J , Dang W , Zurawski G , de Vries J E 
Published: January 2023

Abstract
Recently, we described the cloning and expression of a human cDNA which is the homologue to P600, a gene transcribed by mouse Th2 clones. Based on its activities on human monocytes and B cells this gene was designated IL-13. In the present study we investigated the effects of IL-13 alone or in combination with IL-4, IFN-gamma, or IL-10 on human monocytes. IL-13 induced significant changes in the phenotype of monocytes. Like IL-4, it enhanced the expression of CD11b, CD11c, CD18, CD29, CD49e (VLA-5), class II MHC, CD13, and CD23, whereas it decreased the expression of CD64, CD32, CD16, and CD14 in a dose-dependent manner. IL-13 induced up-regulation of class II MHC Ag and its down-regulatory effects on CD64, CD32, and CD16 expression were prevented by IL-10. IFN-gamma could also partially prevent the IL-13-induced down-regulation of CD64, but not that of CD32 and CD16. However, IL-13 strongly inhibited spontaneous and IL-10- or IFN-gamma-induced ADCC activity of human monocytes toward anti-D coated Rh+ erythrocytes, indicating that the cytotoxic activity of monocytes was inhibited. Furthermore, IL-13 inhibited production of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, macrophage inflammatory protein-1 alpha, granulocyte/macrophage-CSF, granulocyte-CSF, IFN-alpha, and TNF alpha by monocytes activated with LPS. In contrast, IL-13 enhanced the production of IL-1 ra by these cells. Similar results on cytokine production were observed or have been obtained with IL-4. Thus IL-13 shares most of its activities on human monocytes with IL-4, but no additive or synergistic effects of IL-4 and IL-13 on human monocytes were observed, suggesting that these cytokines may share common receptor components. Taken together, these results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities.
Role of gamma delta T cells in murine collagen-induced arthritis.
Authors: Peterman G M , Spencer C , Sperling A I , Bluestone J A 
Published: January 2023

Abstract
Murine collagen-induced arthritis (CIA) is a T cell-mediated disease which is induced by injection of type II collagen. Previous studies have shown that CD4+ cells which express particular V beta TCR genes are involved in the induction of arthritis in this model. In the present report we demonstrate that CD4-, CD8-, TCR gamma delta cells are present in arthritic joints, expanded in peripheral lymphoid tissue of DBA/1 lac J mice with CIA, and respond in vitro to the anti-TCR gamma delta mAb UC7-13D5 (13D5). In order to directly investigate the role of the gamma delta TCR in murine CIA, DBA/1 lac J mice were injected with 13D5 before or 40 days after injection of type II collagen. Our results demonstrate that i.p. injections of 13D5 initiated 1 day before injection of type II collagen significantly delays both the onset and severity of CIA compared with treatment with type II collagen alone. In contrast, anti-TCR gamma delta mAb injection of arthritic mice 40 days after collagen injection resulted in the rapid onset of severe arthritis which was accompanied by increased bone erosion and cell infiltration into inflamed joints compared with arthritic mice injected with either control hamster IgG or F(ab')2 fragments of 13D5. Arthritic mice injected with intact 13D5 rapidly lost weight, suggesting that 13D5 may induce a cytokine-mediated syndrome similar to that observed in mice and humans after the injection of anti-CD3. Flow cytometry analysis of joint cells isolated after collagenase digestion from arthritic mice demonstrated that 13D5 injection induces the accumulation of CD4-, CD8-, PgP-1 (CD44)+ cells within arthritic joints, whereas arthritic joints from mice injected with control hamster IgG contained cells with a CD4+, CD8- phenotype. CD3+ T cell lines which express the gamma delta TCR from inflamed joints of arthritic mice were established and examined for V gamma usage by the polymerase chain reaction. V gamma 2 rearrangements were predominant in both T cell lines established from inflamed synovium as well as freshly isolated synovial cells from arthritic mice, whereas synovial cells from nonarthritic mice did not demonstrate V gamma 2 rearrangements. Taken together, the results described in this report suggest a direct role for gamma delta TCR T cells in the pathogenesis of CIA in DBA/1 lac J mice.
Influence of a recombinant human soluble tumor necrosis factor receptor FC fusion protein on type II collagen-induced arthritis in mice.
Authors: Wooley P H , Dutcher J , Widmer M B , Gillis S 
Published: January 2023

Abstract
A recombinant human TNF receptor Fc fusion protein (rhuTNFR:Fc) was assessed for antiarthritic activity using murine type II collagen-induced arthritis in mice. DBA/1 mice were immunized with bovine type II collagen and treated with rhuTNFR:Fc either from day 21 to day 28 (preventative protocol), or after disease onset for fourteen days (therapeutic protocol). Control mice received either sterile saline or human serum albumin injections. rhuT-NFR:Fc treatment significantly reduced both the incidence and the severity of collagen-induced arthritis in the preventative protocol. Mice receiving rhuTNFR:Fc therapeutically progressed to less severe disease than did control animals, and the arthritis index in rhuTNFR:Fc treated mice was significantly lower than the index in control mice from 7.5 weeks after treatment. The antibody response to collagen was significantly reduced by treatment with rhuTNFR:Fc in both the preventative and therapeutic protocols. No difference was observed in the proliferative response to type II collagen or Con A, but the response to LPS was significantly lower in rhuTNFR:Fc treated mice at the conclusion of both the preventative and therapeutic trials. The results suggest that rhuTNFR:Fc may have both immunosuppressive and antiarthritic properties in this experimental model, and may represent a useful approach to the treatment of autoimmune arthritis.
Induction of transforming growth factor-beta during cardiac allograft rejection.
Authors: Waltenberger J , Wanders A , Fellström B , Miyazono K , Heldin C H , Funa K 
Published: January 2023

Abstract
The polypeptides of the transforming growth factor-beta (TGF-beta) family are potent endogenous immuno-regulators. Using a rat cardiac allograft transplant model, we investigated the expression of the precursor forms of TGF-beta 1, TGF-beta 2, and TGF-beta 3 and the latent TGF-beta binding protein (LTBP) by immunohistochemistry. The activity of TGF-beta in the extracts from transplanted as well as normal hearts was measured using a bioassay, and Northern blot analysis was performed on RNA extracts. The transplanted hearts were analyzed both during acute rejection up to 6 days and during chronic rejection up to 6 mo after transplantation and compared with normal controls. The animals of the chronic rejection group received cyclosporin A for immunosuppression. The TGF-beta bioactivity dramatically increased in the transplanted allografts during the chronic rejection process compared to the normal hearts, and so did the immunostaining as well as the mRNA levels for TGF-beta 1 and, to a lesser extent, the immunostaining for TGF-beta 2. TGF-beta 3 expression remained unchanged and was only found in the myocardium in trace amounts. During the acute rejection process up to 6 days after transplantation, TGF-beta immunoreactivity increased only slightly, whereas the TGF-beta mRNA was severalfold increased. Control animals treated with cyclosporin A showed a similar pattern at day 6 with regard to TGF-beta expression. LTBP was induced simultaneously with TGF-beta 1 and occurred within interstitial spaces of the myocardium. The TGF-beta was produced by macrophage-like infiltrating lymphocytes. In conclusion, highly elevated levels of TGF-beta and LTBP were found during chronic rejection of cardiac allografts in rats. The induction of TGF-beta may counteract the rejection process and could be useful for new therapeutic approaches in the prevention of allograft rejection.
Identification of a transitional preapoptotic population of thymocytes.
Authors: Cohen G M , Sun X M , Snowden R T , Ormerod M G , Dinsdale D 
Published: January 2023

Abstract
Apoptosis, a major form of cell death in the immune system, is characterized by cell shrinkage, chromatin condensation, and cleavage into nucleosomal fragments. Apoptosis may be the mechanism for the elimination of autoreactive and unselected CD4+ CD8+ thymocytes in the thymus. A large number of diverse agents are capable of inducing apoptosis in immature thymocytes. Rat thymocytes were treated with etoposide, a DNA topoisomerase II reactive agent, or dexamethasone, a glucocorticoid, and separated on discontinuous Percoll gradients. We have identified and isolated a transitional preapoptotic population of thymocytes that exhibited early morphologic and biochemical changes associated with apoptosis. These preapoptotic cells were intermediate in size and density between normal and apoptotic thymocytes and exhibited a decreased surface expression of both CD4 and CD8 molecules compared to control thymocytes. On ultrastructural examination, they were shown to possess sharply defined clumps of condensed chromatin abutting onto the nuclear membrane. These morphologic changes, the first detectable signs of apoptosis, occurred prior to the internucleosomal cleavage of DNA, often regarded as the biochemical hallmark of apoptosis. Nucleosomal fragments of 180 to 200 base pairs or multiples thereof were, however, detected following subsequent dramatic changes in the nuclear structure of these preapoptotic cells that resulted in morphology typical of apoptosis. These results suggest that early critical events in apoptosis precede internucleosomal cleavage of DNA.
Analysis of T-cell receptor alpha beta chains of CD8+ suppressor T cells induced by tolerogenic conjugates of antigen and monomethoxypolyethylene glycol. Involvement of TCR alpha-CDR3 domain in immunosuppression.
Authors: Mohapatra S , Chen Y , Takata M , Mohapatra S S , Sehon A H 
Published: January 2023

Abstract
A number of investigators have demonstrated that there exists a relationship between Ag receptors of Ts cells (TCR) and their soluble suppressor factors. With a view to elucidating this relationship, the primary structures of receptors of Ts cells, induced in mice by tolerogenic conjugates of Ag and monomethoxypolyethylene glycol, were characterized in this study. The cDNA encoding the alpha and beta chains of TCR of cloned Ts cells specific for (i) OVA and (ii) human monoclonal (myeloma) IgG (HIgG) were produced by polymerase chain reaction. From the analysis of the V alpha genes of TCR of Ts cells it was deduced that these receptors utilized a new member of the V alpha 15 gene family, which was productively joined to the J alpha genes that differed for each of the Ts cells of the two distinct specificities. Similarly, sequence analysis of the beta chain cDNA of the two Ts cell clones revealed that both clones utilized the V beta 8.2 gene, and that their J beta gene differed from each other. It is inferred that the Ts cells generated in response to the different tolerogenic Ag(mPEG)n conjugates belonged to a subset of T cells utilizing similar TCR alpha beta chains and differed only in their J alpha/J beta regions. Most importantly, pretreatment of mice with a mixture of pentadecapeptides comprising the TCR alpha chain of the OVA-Ts cells, down-regulated the immune response specific to OVA, but not to HIgG. Moreover, injection of mice with a pentadecapeptide corresponding to the CDR3 region of the TCR alpha chain of either OVA-Ts or HIgG-Ts suppressed specifically the Ab response to OVA or HIgG, respectively. On the basis of all these results, it is concluded that the CDR3 of the TCR-alpha chain of Ts cells plays a pivotal role in the Ts network underlying the specific down-regulation of the immune responses induced by tolerogenic Ag(mPEG)n conjugates.
Differential tyrosine-specific protein phosphorylation in mouse T lymphocyte subsets. Effect of age.
Authors: Shi J , Miller R A 
Published: January 2023

Abstract
We have previously reported that activation of normal murine T lymphocytes with either anti-CD3 or Con A leads to increased phosphorylation of three phosphotyrosine-containing proteins with molecular masses of 120, 80, and 40 kDa, that antibody to the alpha beta TCR heterodimer induces phosphorylation of the 120- and 80-kDa species, and that aging impairs phosphorylation of all three substrates. In our study we determine if phosphorylation of these substrates differs among T cell subsets in old and young mice. In young mice, we found that the induced levels of all three phosphorylated substrates, 10 min after addition of the mitogenic stimulus, were significantly higher in CD8 than in CD4 cells for anti-CD3 and Con A stimulation; responses to anti-TCR were also higher in CD8 than in CD4 cells for the 80 kDa, although not the 120-kDa substrate. Aging led to significant declines in the ability to phosphorylate all three substrates in the CD8 population, and also of the 80-kDa substrate in CD4 cells. Comparison of unfractionated CD4 to purified CD4 memory T cells showed that the age-dependent shift from naive to memory T cells could explain the loss with age in p80 phosphorylation, in that memory cells were significantly less able to phosphorylate p80 than were the unseparated CD4 preparations. Phosphorylation of p40 also was significantly lower in CD4 memory cells, as was phosphorylation of p120 in responses to anti-CD3. We conclude that subsets of mouse splenic T cells display different patterns of tyrosine-specific protein phosphorylation in the first 10 min after activation, and that the accumulation of memory T cells with age can account for at least some of the age-dependent decline in tyrosine protein kinase pathways.
The human VH3b gene subfamily is highly polymorphic.
Authors: Adderson E E , Azmi F H , Wilson P M , Shackelford P G , Carroll W L 
Published: January 2023

Abstract
We have previously shown that human antibody (Ab) directed against the capsular polysaccharide of the important bacterial pathogen, Haemophilus influenzae type b (Hib) is encoded by a small group of VH3 gene family members. The majority of anti-Hib PS Ab use members of the smaller VH3b subfamily. To examine directly the available human VH3 repertoire, we have used PCR to amplify and clone candidate germ-line VH3b H chain V region genes from two unrelated subjects from whom anti-Hib polysaccharide mAb had been previously obtained. A single functional VH3b germ-line gene was obtained from one subject. This gene is identical throughout the coding region to the previously identified gene 9.1. Twelve distinct VH3b germ-line sequences, 87.6-99.8% homologous to one another, were obtained from the second subject. One of these genes, LSG1.1, is also identical to the 9.1 germ-line gene, and a second, LSG6.1, is identical to a previously reported cDNA, M85. These germ-line VH3b genes are 82.7-94.1% homologous to rearranged anti-Hib PS VH3b segments obtained from these subjects. Our findings further demonstrate that considerable polymorphism of VH segments exists in the human population. Despite the presence of very highly homologous VH elements in the germ line, particular genes are highly conserved within the outbred human population.
Functional identification of transcription control sequences of the mouse Crry gene.
Authors: Martin B K , Weis J H 
Published: January 2023

Abstract
The mouse C receptor-related gene Crry is expressed by a wide variety of cells. Those sequences required for the transcriptional control of this gene were identified by deletion analysis of regions 5' of the initiating ATG. Fusion of Crry promoter sequences to the reporter gene CAT identified a region approximately 1,500 bp upstream of the transcriptional start site that enhanced transcription of this gene construct. Gel shift and methylation interference assays were performed, and a specific protein-DNA complex was identified within this region. These assays defined a 16-bp sequence 1,642 bp 5' of the initiating ATG that bound a protein in nuclear extracts prepared from all murine cell lines and tissues examined. The methylation interference assay indicated that the core region of the DNA sequence recognized by the protein was GGAA, the common core binding site for the ets family of proto-oncogenes. Oligonucleotides prepared from this sequence with the GGAA sequence did inhibit the DNA/protein complex formation, whereas those with a mutant GGAA sites did not. The minimal site identified by methylation interference was able to up-regulate transcription when placed downstream of a heterologous promoter, whereas the same sequence with an altered GGAA site could not. Thus, this site functions as an enhancer.
Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells.
Authors: Allman D M , Ferguson S E , Lentz V M , Cancro M P 
Published: January 2023

Abstract
HSAhi B cells comprise 5 to 10% of adult mouse splenic B cells and are phenotypically and functionally immature. To assess their origin and relationship to mature, heat-stable Ag (HSA)lo B cells, we determined HSA and surface IgD phenotype among splenic B cells throughout development, as well as during reconstitution of lethally irradiated adults given adult B-depleted bone marrow. In each case, HSAhi splenic B cells predominate during the earliest stages of B cell genesis. Furthermore, 5-bromo-2'-deoxyuridine labeling experiments indicate rapid turnover within both the marrow and peripheral HSAhi pools, and adoptive transfer studies show that peripheral HSAhi splenic B cells differentiate to HSAlo within 4 days. Finally, splenic HSAhi B cells reconstitute both primary and memory humoral responses. Together, these data indicate that splenic B cells in the HSAhi subset are an intermediate maturational stage in the adult periphery.
Lipopolysaccharide and tumor necrosis factor-alpha induce lipopolysaccharide receptor expression on bone marrow cells by different mechanisms.
Authors: Chaby R , Pedron T , Stütz P L , Girard R 
Published: January 2023

Abstract
Two cell types, monocytes/macrophages and neutrophilic granulocytes, play a prominent role in the pathogenic effects of endotoxins during Gram-negative infections. We previously established that nanomolar concentrations of LPS induce the expression of new specific LPS-binding sites (LpsR) in bone marrow granulocytes of LPS-responsive mice. To examine this induction process further, we asked whether it, like other LPS activities, can be mediated by TNF-alpha. We report that exogenous rTNF-alpha can induce LpsR expression in bone marrow cells (BMC) from both LPS-responsive (C3H/HeOU) and LPS-hyporesponsive (C3H/HeJ) mice. In BMC, LPS elicited a down-regulation of the TNF-alpha receptors (TNF-R) without direct binding to TNF-R. On the other hand, taxol, a microtubule stabilizer that has shown LPS mimetic activity in macrophages, was unable to elicit LpsR expression or induce TNF-R down-regulation in BMC. Thus, unlike the LPS-signaling receptor of macrophages, that of BMC is apparently not functionally associated with microtubules. The LPS-induced expression of LpsR was inhibited only partially with an anti-TNF-alpha serum, and with dexamethasone, suggesting that an autocrine activity of endogenous TNF-alpha cannot alone account for the LPS effect. Comparative analyses also indicated that dexamethasone inhibited the LPS-induced increase of LpsR, but enhanced the number of TNF-induced LpsR+ BMC. Furthermore, the synthetic lipid PPDm2 (a 1,4-bisphosphorylated and N,N-diacylated derivative of 2,3-diamino-2,3-dideoxy-D-glucose) inhibited LPS-induced, but not TNF-induced, expression of LpsR. These data show that in BMC, LPS and TNF-alpha induce LpsR expression by different mechanisms.