bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in lymphopoiesis after hematopoietic reconstitution with IL-7 virus-infected bone marrow.
Authors: Fraser C C , Thacker J D , Hogge D E , Fatur-Saunders D , Takei F , Humphries R K 
Published: December 2022

Abstract
Murine bone marrow was infected with a helper-free recombinant retrovirus expressing the mIL-7 gene and used to reconstitute lethally irradiated hosts. Twenty-three percent of mIL-7 retrovirus-infected recipients became moribund within 4-16 wk posttransplant with splenomegaly and hyperplastic lymph nodes, elevated white blood cell counts, plus other noticeable abnormalities including, in one animal, lymphocytic ascites. FACS analysis of hematopoietic tissue in diseased mice revealed marked alterations in T cell subsets of spleen and lymph nodes. These differences in extrathymic tissues compared with control animals included increases in CD4(-)-CD8+ lymphocytes and most strikingly the appearance of large numbers of an unusual CD4(+)-CD8+ T cell population with other characteristics of immature thymocytes (CD3lo-Thy1(+)-HSAhi). 3H-thymidine incorporation assays performed on extrathymic lymphocytes from a lymph node or ascites of two affected mice showed high levels of proliferation in the absence of either CD3 cross linking or exogenous IL-7 stimulation. Interestingly, in contrast to the effects noted on peripheral lymphoid tissues, no alteration in thymic size was noted and the proportion of CD4(+)-CD8+ cells was generally decreased with corresponding increases in CD4+ or CD8+ or CD4(-)-CD8- cells. These results provide further evidence of the involvement of IL-7 in the development and proliferation of early T cells in vivo and point to the possibility of IL-7 involvement in extrathymic expansion of a primitive class of T cells, the functional nature of which remains to be elucidated.
Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes.
Authors: Postigo A A , Sánchez-Mateos P , Lazarovits A I , Sánchez-Madrid F , de Landázuri M O 
Published: December 2022

Abstract
Cell-cell and cell-extracellular matrix interactions are mediated by a wide array of cell surface molecules known as adhesion receptors, including the integrin family that comprises numerous alpha beta heterodimers. A new integrin group, the beta 7 subfamily, has been recently defined. Its two members, alpha 4 beta 7 and alpha H beta 7, are involved in the lymphocyte migration to the Peyer's patches and the intestinal mucosa, respectively. We have analyzed the expression of alpha 4 beta 7 integrin on B cells from different cellular compartments and at different activation states. Resting peripheral blood B lymphocytes constitutively express large amounts of alpha 4 beta 7. By contrast, alpha 4 beta 7 integrin, which is absent on resident B cells from different lymphoid tissues, is induced upon activation. Functional studies indicates that alpha 4 beta 7 is mediating B cell attachment to fibronectin and vascular cell adhesion molecule-1 through distinct epitopes on this integrin. Furthermore, the alpha 4 beta 7 integrin is also implicated in intercellular interactions as deduced by the ability of anti-alpha 4 beta 7 mAb to trigger homotypic B cell aggregation. Finally, alpha 4 beta 7 and alpha 4 beta 1 integrins redistribute at the cell membrane in a similar clustering pattern when B cells attach to fibronectin- and vascular cell adhesion molecule-1-coated surfaces. Our studies demonstrate the differential regulation on the expression and function of alpha 4 beta 7 integrin among different human B cell populations.
Stimulation of IL-2 production in murine lymphocytes by substance P and related tachykinins.
Authors: Rameshwar P , Gascon P , Ganea D 
Published: December 2022

Abstract
Substance P (SP), a tachykinin neuropeptide, has been previously reported to stimulate IL-2 production in murine T cell lines activated with phorbol esters. Here we extend these observations by establishing the stimulatory effect of SP and related tachykinins on IL-2 production by normal murine lymphocytes and on purified CD4+ T cells. SP proved to be the most efficient IL-2 inducer, exerting its maximal effect at concentrations that were 4 to 5 orders of magnitude lower than the optimal stimulatory concentrations of physalaemin, NKA, or NKB. SP stimulated IL-2 production in a dose-dependent manner, with an optimal concentration range of 10(-10) to 10(-14) M, comparable with physiologic concentrations of SP found in blood and other organs. The effect of SP was carried by the carboxyl-terminal part of the molecule (SP4-11). The specificity of SP activity was confirmed by the inhibitory effect of spantide, a tachykinin antagonist, and of CP-96,345, a nonpeptide antagonist specific for NK-1-type receptors. In unfractionated spleen cell cultures SP induced de novo IL-2 protein synthesis. SP could induce IL-2 production either directly, or in combination with Con A or anti-CD3 antibody treatments. The effect of SP in conjunction with Con A was synergistic, whereas the effect in conjunction with anti-CD3 antibodies was additive, suggesting different molecular mechanisms for these stimulatory factors. In the absence of additional costimuli the effect of SP in unfractionated spleen cell cultures was partially mediated through the induction of IL-1, and both SP and IL-1 were required for IL-2 induction in purified CD4+ T cells. In contrast to its stimulatory effect on the generation of IL-2, SP did not induce IFN-gamma production in murine spleen cells. The stimulatory effect of SP on IL-2 production suggests that some of the already described immunostimulatory activities of SP could be mediated through the up-regulation of IL-2 production in normal lymphocytes.
The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD4+ T cells.
Authors: Roy M , Waldschmidt T , Aruffo A , Ledbetter J A , Noelle R J 
Published: December 2022

Abstract
Studies have established that gp39, the ligand for CD40, induces B cell cycle entry and is involved in the initiation of the humoral immune response. Expression of gp39 has been observed on normal, activated CD4+ T cells, activated lymph node cells; an activated Th1 clone, and an activated Th2 clone. Anti-CD3-activated CD8+ T cells did not express gp39; however, CD8+ T cells activated with PMA/ionomycin expressed gp39. The kinetics of anti-CD3-induced gp39 expression on a T cell clone and on splenic CD4+ T cells showed that gp39 was detectable at 4 h after activation, reaching maximal levels between 6 to 8 h postactivation and returning to near resting levels between 24 to 48 h. Lymphokines modulated the expression of gp39 on activated T cells. Expression of gp39 was inhibited by IFN-gamma on activated Th1, Th2, and CD4+ T cells; whereas TGF-beta inhibited gp39 expression only on the Th2 clone studied. All other lymphokines tested were without substantial effect. Differences in the expression of gp39 on activated naive and memory T cells were observed, as well as differences in requirements for optimal gp39 expression on these subsets. There are correlations between gp39 expression and effector function; however, anti-CD3-activated splenic CD4+ cells that express gp39 did not exhibit effector function. A comparison of the relative numbers of molecules of gp39 shows that activated Th1 clones express at least 20-fold the number of gp39 molecules/cell compared with activated splenic CD4+ cells. This may imply that density of gp39 on the activated T cells plays an important role in determining effector function.
Presentation of the Mls-1 superantigen by human HLA class II molecules to murine T cells.
Authors: Subramanyam M , McLellan B , Labrecque N , Sekaly R P , Huber B T 
Published: December 2022

Abstract
Superantigens (SAG) presented in the context of MHC class II proteins stimulate a strong proliferative response in T cells expressing particular TCR V beta genes. Although this T-cell recognition is not MHC restricted, a strong hierarchy is observed in the ability of various MHC class II molecules to present SAG. Mls-1, encoded by the Murine Mammary Tumor Virus (MMTV) Mtv-7 sag gene, is the prototype of endogenous SAG. In the present study, we have analyzed whether this retroviral gene product can be presented in the context of human HLA class II proteins to murine T cells. Positive results were obtained with the DR isotype and in in vitro, as well as in vivo T-cell stimulation assays. However, the various DR beta alleles, expressed in combination with an identical DR alpha chain, differed in their Mls-1 presenting capacity, indicating that the MHC class II beta-chain contains the primary contact site for Mls-1. Interestingly, the same pattern of TCR V beta restriction was seen in response to Mls-1 presented in the context of human and mouse class II, suggesting that the TCR V beta specificity is uniquely determined by the retroviral SAG. Furthermore, Mls-1 presented in the context of the DQw1 and DPw2 isotypes did not elicit a T-cell response. The results from this study form the basis for further analysis of the exact region in the class II beta-chain that interacts with Mls-1.
Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction.
Authors: Yin T , Taga T , Tsang M L , Yasukawa K , Kishimoto T , Yang Y C 
Published: December 2022

Abstract
IL-11 is a novel cytokine with a variety of biofunctions which overlap with those of IL-6. We have previously identified IL-11 specific binding protein which is distinct from that of IL-6 in a number of cell lines. The similarities in biofunctions and differences in ligand binding proteins between IL-11 and IL-6 prompted us to investigate whether IL-11 shares common signal transduction mechanisms with IL-6. We have examined early signals triggered by IL-11 or IL-6 in a multifactor-dependent human erythroleukemic cell line, TF-1. The results showed that IL-11 and IL-6 can both stimulate cell proliferation, induce similar pattern of protein tyrosine phosphorylation, and activate the same proto-oncogene (junB) expression in TF-1 cells. These findings imply that IL-11 and IL-6 share similar early signaling events with the possibility of using the same signal transducer, gp130. We next tested whether IL-11 induced signaling can be inhibited by anti-gp130 antibodies which blocked IL-6-mediated functions. It was observed that anti-gp130 antibodies abolished cell proliferation, protein tyrosine phosphorylation, and junB gene expression elicited by IL-11 or IL-6 in TF-1 cells. The same antibodies, however, had no effect on granulocyte-macrophage colony stimulating factor or erythropoietin-induced TF-1 cell proliferation. Finally, anti-IL-6R antibody inhibited the ability of IL-6, but not IL-11, to transduce early signals in TF-1 cells. These results demonstrate that IL-11 and IL-6 utilize different ligand binding proteins, but share common signal transducer, gp130, in TF-1 cells.
Nonimmune macromolecular complexes of Ig in human gut lumen. Probable enhancement of antibody functions.
Authors: Bouvet J P , Pirès R , Iscaki S , Pillot J 
Published: December 2022

Abstract
Protein Fv, a human sialoprotein recently described in the stools of patients suffering from liver diseases, binds the variable domain of H chains without impairing Ag binding. Normal subjects are shown here to secrete protein Fv under a hidden form, saturated with luminal Ig. In feces, the nonimmune complexes are essentially of 1800 and 800 kDa M(r); they contain protein Fv molecules bound with F(ab')2 fragments produced by cleavage of Secretory IgA during colonic transit. The 800-kDa complexes correspond to 6 molecules of F(ab')2 fragments bound to a sole protein Fv dimer. This was established by comparison with an in vitro-made complex having a valency of 6. Investigation of the role of protein Fv shows that in vitro addition of this free molecule to antivirus or to anti-Salmonella typhi antibodies allows or augments agglutination of the corresponding pathogens. This property is of major interest for secretory antibodies because it favors their role in Ag conveyance in the mucus stream. It seems therefore that protein Fv is a novel key factor of the immune defense in gut.
Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells.
Authors: Yamamoto N , Kumashiro R 
Published: December 2022

Abstract
Highly conserved DBP (human DBP is known as Gc) of serum alpha 2-globulin fraction can be converted to a potent macrophage activating factor by stepwise modification of Gc glycoprotein with beta-galactosidase of B cells and sialidase of T cells. These glycosidases, beta-galactosidase and sialidase, are membrane bound and not soluble in culture medium. Thus, consecutive contact of Gc protein with B cells and T cells, presumably via specific receptors, is required for conversion of Gc glycoprotein to the macrophage activating factor. The essential role of T cell sialidase in macrophage activation was confirmed by the finding that peritoneal nonadherent cells of SM/J mouse, whose T cells are deficient in sialidase activity, were unable to convert Gc protein to the macrophage activating factor and thus did not activate macrophages. Treatment with sialidase of a conditioned medium of lipid metabolite-treated SM/J mouse nonadherent cells efficiently generated the macrophage activating factor. When Gc protein was first treated with soluble or immobilized sialidase and used in a medium for 2 h cultivation of lipid metabolite-treated SM/J mouse nonadherent cells or BALB/c mouse B cells, the resultant conditioned media contained a large amount of the macrophage activating factor. These results support the hypothesis that Gc protein carries a dibranched trisaccharide with galactose and sialic acid termini.
Differential expression of H-2K and H-2D in the central nervous system of mice infected with Theiler's virus.
Authors: Altintas A , Cai Z , Pease L R , Rodriguez M 
Published: December 2022

Abstract
A model of demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) was used to study differential regulation of class I MHC gene products in the brain and spinal cord of resistant (B10) and susceptible (B10.Q and B10.RBQ) mice. Allelic polymorphisms in the H-2D region, but not the H-2K region, play a primary role in determining susceptibility to late demyelinating disease. However, even though significant structural diversity distinguishes class I alleles, there are no discernible K or D-specific patterns of structural diversity within the peptide binding domains of these glycoproteins. Our hypothesis was that D region association of susceptibility to demyelination was related to differences in the expression of the K and D Ag in the central nervous system (CNS) after TMEV infection. Using allele-specific mAb and an immunoperoxidase technique, we demonstrated transient but equivalent increases in K and D Ag expression in the brain and spinal cord of resistant mice beginning 7 days after TMEV infection, which returned to baseline by 90 days. However, when genetically susceptible animals were examined, a significantly greater increase in D expression relative to K expression was seen in the brain and spinal cord at all post-infection observation periods. Immunosuppression of genetically resistant animals before TMEV infection, which results in viral persistence, was accompanied by equivalent increases in both the K and D Ag. Depletion of CD8+ T cells, but not CD4+ T cells, in susceptible mice ablated class I expression in the CNS in response to TMEV infection, implying that CD8+ cells contribute to the differential regulation of K and D Ag in the CNS. These findings are consistent with the hypothesis that differences in gene regulation may account for different roles of the K and D loci play in determining resistance and susceptibility to TMEV-induced demyelinating disease.
High affinity, thyroid-specific human autoantibodies displayed on the surface of filamentous phage use V genes similar to other autoantibodies.
Authors: Portolano S , McLachlan S M , Rapoport B 
Published: December 2022

Abstract
Autoantibodies to thyroid peroxidase (TPO) are characteristic of thyroid inflammation in autoimmune thyroid disease. We have used the phage display, H and L chain combinatorial cDNA library approach to clone, from thyroid-infiltrating B cells, six new human Fab autoantibodies with high affinities (approximately 10(-10) M) for TPO. This library, in the pComb3 vector, was screened with viable, stably transfected Chinese hamster ovary cells expressing human TPO on their surface. The H and L chain genes in the six TPO-specific Fab were similar, but not identical, to those encoding Fab previously isolated from the same library by screening bacteriophage plaques in the Immunozap vector with purified TPO. The TPO-specific VK genes isolated with the phage display system are closer to germline than those obtained with Immunozap. Essentially all the V kappa isolated with pComb3 were 99 or 100% homologous with the germ-line genes KL012 and A3 that also code for low affinity systemic autoantibodies. There are two important implications of the study. First, the phage display system can be used with impure Ag to generate high affinity autoantibodies. This finding opens the way to cloning autoantibodies against other autoantigens, not previously possible with the bacteriophage lambda approach because of the lack of purified Ag. Second, germ-line L chain genes can code for very high affinity antibodies.
Heterogeneous mechanisms of human cytotoxic T lymphocyte generation. II. Differential effects of IL-6 on the helper cell-independent generation of CTL from CD8+ precursor subpopulations.
Authors: Bass H Z , Yamashita N , Clement L T 
Published: December 2022

Abstract
The subpopulations of CD8+ T cells defined by CD45RA Ag expression have been hypothesized to represent cells varying in their relative maturation along a common, activation-dependent differentiation pathway. Although both the CD8+CD45RA+ and CD8+CD45RA- subsets contain precursor cells that can develop into alloreactive CTL, these subsets differ in their ability to produce and use IL-2, a cytokine that is essential for T helper cell-independent CTL generation. In these studies, we have characterized the ability of these CD8+ subsets to undergo CTL differentiation in response to IL-6, another cytokine reported to be important or even essential for CTL generation. Purified CD8+CD45RA+ or CD8+CD45RA- cells were stimulated with allogeneic B cell lines, either alone or in the presence of exogenous cytokines. Alloactivated CD8+CD45RA- cells failed to differentiate into cytotoxic cells in the presence of IL-6 alone. In contrast, IL-6 stimulated the differentiation of antigen-specific CTL from alloactivated CD8+CD45RA+ precursors. The mechanism underlying this helper cell-independent process appeared to require IL-2, because IL-6-mediated CTL generation was abrogated by anti-CD25 or anti-IL-2 antibodies. Although CD8+CD45RA- cells did not respond to IL-6 alone, these cells were able to respond to IL-6 in a synergistic fashion in the presence of suboptimal concentrations of exogenous IL-2. These studies demonstrate that the CD8+ precursor subsets defined by CD45RA expression differ in their ability to undergo IL-6-mediated helper cell-independent CTL generation. Our data further suggest that this functional dissimilarity results from putative maturation-linked differences in the ability of these CD8+ precursor cells to produce IL-2.
The CD19 signal transduction complex of B lymphocytes. Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13.
Authors: Bradbury L E , Goldmacher V S , Tedder T F 
Published: December 2022

Abstract
CD19 expressed on the surface of B lymphocytes is a key member of a cell surface signal transduction complex that includes TAPA-1, Leu 13 and CD21. The human CD19 protein is composed of 540 amino acids with a cytoplasmic domain of 242 amino acids. Although the cytoplasmic domain of CD19 has no sequence homology with other proteins, the cytoplasmic domain of human, mouse, and guinea pig CD19 is highly conserved suggesting that this region of CD19 is at least partially responsible for signaling activity. In this study, the regions of CD19 required for intermolecular associations and signal transduction were determined by comparing a series of carboxyl-terminal cytoplasmic tail deletion mutants and a CD19/L-selectin chimera with native CD19. CD19 expressed in the human Rex T cell line and the K562 erythroleukemia cell line generated transmembrane signals and also associated with endogenous TAPA-1. Deletion of 95% of the CD19 cytoplasmic domain did not affect the ability of CD19 to be expressed or to associate with TAPA-1. However, replacement of the CD19 transmembrane and cytoplasmic domains with those of L-selectin (CD19-LAM) resulted in the loss of CD19 complex formation, suggesting that the membrane spanning domain is critical for this association. Similarly, the induction of homotypic adhesion through CD19 or truncated CD19 was equivalent, whereas homotypic adhesion was not induced via the CD19-LAM chimera. In addition, the cytoplasmic domain was not necessary for CD19 mAb-mediated growth inhibition or internalization. In contrast, the CD19 cytoplasmic domain was required for optimal mAb-induced increases in [Ca2+]i in CD19 cDNA-transfected Rex cells. Thus, the CD19 cytoplasmic domain is responsible for the induction of increased [Ca2+]i, and the transmembrane region is required for cell surface associations with the other members of the CD19 complex and most signaling events. Therefore, mAb binding to CD19 is likely to initiate multiple intracellular signal transduction cascades either through CD19 directly, or through other members of the CD19 complex.