bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine regulates the respiratory burst of cytokine-triggered human neutrophils adherent to biologic surfaces.
Authors: de la Harpe J , Nathan C F 
Published: December 2022

Abstract
The effect of adenosine on the respiratory burst was investigated using human neutrophils adherent to serum-coated surfaces. Adenosine caused complete suppression of the respiratory burst elicited by TNF-alpha, FMLP, or CSF for granulocytes; partial suppression of the response to CSF for granulocytes/macrophages, Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, or uncoated polystyrene surfaces; and no suppression of the response to PMA. In most experiments, 4.7 x 10(-7) M and 2.5 x 10(-8) M adenosine caused 50% suppression of H2O2 release in response to TNF-alpha and FMLP, respectively, and 10 microM caused 100% suppression. Preexposure of neutrophils to ADP blocked the inhibitory effect of adenosine. With adherent neutrophils, there is a prolonged lag period in the onset of the respiratory burst in response to cytokines. Adenosine was fully suppressive if its addition was delayed past the first third of this lag period, or if it was removed during the last third of the lag period. A 10-min pulse with adenosine was most inhibitory when delivered in the middle third of the lag period. Dihydrocytochalasin B abolished the suppressive effect of adenosine on H2O2 release in response to FMLP. Thus adenosine, at concentrations found in human plasma, is a potent but selective inhibitor of the respiratory burst of adherent human neutrophils in response to physiologic, soluble stimuli, and ADP is a potentially physiologic counter-suppressant. Adenosine appears to exert most of its effect during a discrete interval within the lag period before onset of the respiratory burst, and may affect the coupling of agonist receptors to the cytoskeleton.
Effects of treatment with IL-2 receptor specific monoclonal antibody in mice. Inhibition of cytotoxic T cell responses but not of T help.
Authors: Leist T P , Kohler M , Eppler M , Zinkernagel R M 
Published: December 2022

Abstract
Contribution of IL-2R-bearing activated lymphocytes to antiviral host defense was investigated in C57BL/6 mice by treatment in vivo with IL-2R-specific mAb PC61. When treated on days 0 and 1 with respect to infection with either vaccinia virus, lymphocytic choriomeningitis (LCM) virus (LCMV) or vesicular stomatitis virus, 6-day immune mice had low numbers of CD8+ T cells that were reduced to about 10% of the values found for infected but otherwise untreated controls. In contrast, the number of CD4+ T cells was within normal ranges. Correspondingly, induction of strictly T help-dependent antiviral neutralizing IgG antibody titers remained unaffected by the mAb treatment, whereas generation of antiviral cytotoxic T cell activity was abrogated. Anti-IL-2R treatment of thymectomized mice 14 and 15 days after infection prevented generation of secondary antiviral cytotoxic T cells in restimulation cultures in vitro initiated 24 days later. Treatment with IL-2R-specific mAb was comparable to treatment with CD8-specific mAb in preventing mice to eliminate virus. Because of the involvement of antiviral cytotoxic T cells in disease manifestations, treatment with IL-2R-specific mAb protected mice from lethal LCM after intracerebral infection with LCMV and inhibited the footpad swelling reaction caused by local infection with the same virus.
Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses.
Authors: Cairns E , Kwong P C , Misener V , Ip P , Bell D A , Siminovitch K A 
Published: December 2022

Abstract
In order to investigate the genetic basis for natural anti-DNA immune responses, we isolated and sequenced the variable gene elements (VH and VL) encoding an anti-DNA antibody expressed by a human hybridoma of normal origin (Kim4.6) and compared these sequences with those reported for four other human anti-DNA antibodies. The Kim4.6 antibody leader and VH segments were identical in nucleotide sequence with the VH1.9III germ-line VH3 gene, and the Kim4.6VL segment showed 98% nucleotide sequence identity with a V lambda I subgroup gene expressed in a Burkitt's lymphoma. Comparative analysis of Kim4.6 and other human hybridoma anti-DNA antibodies indicated that anti-DNA immune responses are diverse in terms of VH and VL gene utilization but may exhibit a bias toward rearrangement of VH genes that are over-represented in the fetal pre-B cell repertoire. Moreover, Kim4.6 and three of four other sequenced human anti-DNA antibodies appear to use a germ-line diversity gene, DXP'1, which may represent a counterpart of the DFL16.1 segment utilized in murine responses to the hapten nitrophenyl. Taken together, our findings indicate that anti-DNA immune responses can be encoded by nonmutated VH genes and that the elements and molecular mechanisms which engender this response are essentially the same among natural and lupus-associated anti-DNA antibodies. Our data also suggest that natural autoimmune responses originate early in B cell ontogeny as is consistent with the hypothesis that autoreactivity plays a major role in shaping the normal immune repertoire.
Ig V region gene expression in small lymphocytic lymphoma with little or no somatic hypermutation.
Authors: Pratt L F , Rassenti L , Larrick J , Robbins B , Banks P M , Kipps T J 
Published: December 2022

Abstract
Using the polymerase chain reaction we examined for specific Ig kappa-L chain V region gene (V kappa gene) rearrangement in small lymphocytic non-Hodgkin's lymphomas that express Ig bearing a major kappa-L chain associated cross-reactive Id, designated 17.109. Previously, we identified the 17.109-cross-reactive Id in chronic lymphocytic leukemia as a serologic marker for expression of a highly conserved V kappa gene, designated Humkv325. Using sense-strand oligonucleotides specific for the 5'-end of this V kappa gene and antisense oligonucleotide specific for a J kappa region consensus sequence, we could amplify specifically Humkv325 when juxtaposed with J kappa through Ig gene rearrangement. This allowed us to amplify rearranged V kappa genes from DNA isolated from minute amounts of lymphoma biopsy material for molecular analyses. Our studies demonstrate that 17.109-reactive SL NHL, with or without associated CLL, rearrange, and presumably express, Humkv325 without substantial somatic diversification. Our data suggest that malignant B cells in SL NHL, in contrast to NHL of follicular center cell origin, may express immunoglobulin variable region genes with little or no somatic hypermutation.
Identification of a human natural killer cell target cell antigen with monoclonal antibodies.
Authors: Harris D T , Jaso-Friedmann L , Devlin R B , Koren H S , Evans D L 
Published: December 2022

Abstract
mAb have been derived against NK cell-sensitive target cells in an effort to identify the target cell structure involved in Ag recognition by NK cells. Several mAb were selected for further study based on their preliminary target cell binding characteristics. Flow cytometry demonstrated that each of these mAb bound to a series of NK-sensitive target cells of various origins (e.g., K562 and Molt-4) while having little or no reactivity with several NK-resistant target cell lines (e.g., SB and Daudi). Functional studies revealed that two of the mAb were able to inhibit the lysis of NK-sensitive K562 target cells by freshly isolated, endogenous NK cells in a dose-dependent fashion. Further, these mAb also could inhibit the killing of K562 target cells by both activated NK cells and cultured lymphokine-activated killer cells, as well as the cytolysis of other NK-sensitive target cells by each of these effector cell populations. Control experiments with another mAb which bound to the target cells but did not inhibit lysis implied that the effects of these mAb on NK cell function was not the result of steric hindrance. Single cell conjugate assays demonstrated that the mAb inhibited NK cell lysis via the inhibition of binding (recognition). Biochemical analysis of this target cell structure revealed that it was a molecule of approximately 42 kDa which may exist as a homodimer in its native state. Thus, it appears that the mAbs identify an unique Ag on the surface of NK cell-sensitive target cells which is involved in NK cell Ag recognition.
Mutation of 3' splice sites in two different class I genes results in different usage of cryptic splice sites.
Authors: Hedley M L , Forman J , Tucker P W 
Published: December 2022

Abstract
To determine the pattern of alternative splicing at the 5' end of class I genes, the 3' splice sites bordering exon 2 of the H-2Dd and H-2Kd genes were mutated from AG to GG (H-2Dd) or CG (H-2Kd). The mutant genes were transfected into L cells, and RNA from clones expressing these Ag was used for analysis by RNase and S1 nuclease mapping techniques. The first intervening sequence of both class I genes contains several potential 3' splice acceptor sites. However, a clear preference for only one site was detected in each of the H-2Dd and H-2Kd mRNA. Examination of the endogenous H-Dd and H-2Kd class I transcripts in normal murine tissues and in tumors demonstrated that the alternatively spliced mRNAs were produced, but at a low frequency. Infection of transfected L cells or tumor lines with vesicular stomatitis virus altered the level of differentially spliced message in these cells.
Inhibition of lymphokine-activated killer- and natural killer-mediated cytotoxicities by neutrophils.
Authors: Shau H Y , Golub S H 
Published: December 2022

Abstract
Peripheral blood polymorphonuclear neutrophils (PMN) can significantly inhibit lymphokine-activated killer- (LAK) mediated cytotoxicity when added to a cytotoxicity assay of IL-2-activated PBL and target cells. The inhibition by resting PMN is resistant to blocking with catalase and superoxide dismutase, suggesting that reactive oxygen species are not involved. The addition of TNF greatly enhanced the PMN-mediated inhibition of LAK effector functions. This TNF-enhanced inhibition is reversed by catalase, but not by superoxide dismutase, implicating hydrogen peroxide in the augmented inhibition. Separation of PMN from effector cells and target cells totally abrogates the inhibition by both resting PMN and TNF-treated PMN. Formalin-fixed PMN, heat-treated PMN, PMN lysates, and PMN membrane all fail to mediate any inhibition of LAK. These results suggest that contact with intact viable PMN is needed for inducing LAK inhibition. However, pretreatment of LAK cells with PMN also decreases their cytotoxicity in subsequent chromium release assays. PMN can also inhibit NK cytotoxicity of fresh PBL. However, NK activity is much less sensitive to inhibition by resting PMN than is LAK. TNF also augments PMN inhibition of NK, and there is no significant difference between LAK and NK in sensitivity to the TNF-enhanced inhibition. Our results indicate that PMN can significantly influence the destruction of tumor targets by LAK and NK, and suggest that approaches to circumvent such regulation may be important in the outcome of immunotherapies with IL-2 and LAK cells.
Transferrin receptor synthesis is an early event in B cell activation.
Authors: Futran J , Kemp J D , Field E H , Vora A , Ashman R F 
Published: December 2022

Abstract
Purified, small resting mouse B cells appear to express low levels of transferrin receptor (TfR) as detected by flow cytometry. Moreover, when such cells are stimulated with LPS or F(ab')2 anti-mu, they show increased expression of TfR as early as 4 h after activation when the cells are at the boundary of G0 and G1 phase by cell cycle analysis. Cells treated with anti-mu increased TfR expression gradually, reaching a plateau after 46 h, whereas cells with LPS reached their plateau by 12 h. The kinetics of induction of increased TfR expression was similar for both small and large B cells. Inhibition of protein synthesis with anisomycin or inhibition of transcription with actinomycin-D blocked the increased expression of TfR at 4 h. Northern blot analysis showed a marked increase of TfR mRNA at 2 and 4 h with either anti-mu or LPS which was then followed by an apparent decline at 16 h. These findings together with other recent studies justify reevaluation of the generally accepted models placing TfR induction late in the G1 phase of the lymphocyte activation sequence. They support the concept that in the B lymphocyte the TfR gene is selectively transcribed earlier than previously thought, before the general increase in RNA synthesis.
Clonogenic potential of murine CD4+8+ thymocytes. Direct demonstration using a V beta 6-specific proliferative stimulus in Mlsa mice.
Authors: Howe R C , MacDonald H R 
Published: December 2022

Abstract
Although considerable indirect evidence supports the hypothesis that CD4+8+ thymocytes are developmental intermediates in the generation of mature (CD4+8- or CD4-8+) T cells, the ability of these cells to proliferate in vitro has been highly controversial. We demonstrate here that a fraction of purified murine CD4+8+ thymocytes can be induced to proliferate in response to immobilized anti-TCR mAb. To exclude possible proliferation by trace mature T cell contaminants, we have exploited our recent finding that in Mlsa mice mature V beta 6-bearing thymic T cells are virtually absent (less than or equal to 0.5%) due to clonal deletion, whereas V beta 6 +CD4+8+ thymocytes are present in much higher numbers (approximately 3%). Proliferation of sorted CD4+8+ thymocytes from Mlsa mice was therefore induced at limiting dilution with immobilized anti-V beta 6 mAb to select against any contaminating mature T cells. Under optimal culture conditions, the frequency of CD4+8+ thymocytes proliferating specifically to anti-V beta 6 mAb (1/1000) was higher than those obtained for purified CD4-8+ (1/2000) or CD4+8- (1/5000) subsets, thus demonstrating directly that a proportion (in this case 3%) of CD4+8+ thymocytes are potentially clonable. During culture, V beta 6 +CD4+8+ thymocytes gave rise to a mixture of phenotypically "immature" (CD4-8-) and "mature" (CD4-8+) T cells. This system should be valuable for further analysis of the elusive CD4+8+ thymocyte subset.
CD44 contributes to T cell activation.
Authors: Huet S , Groux H , Caillou B , Valentin H , Prieur A M , Bernard A 
Published: December 2022

Abstract
We demonstrate here that the CD44 molecule, which mediates lymphocyte adhesion to high endothelial venules (HEV), is also involved in the delivery of an activation signal to the T cell. We have produced a CD44 mAb (H90) which is able to block the binding of lymphocytes to high endothelial venules. H90 had no effect on [3H]TdR incorporation of whole PBL stimulated by lectins, allogeneic cells, or CD3 mAb in the soluble phase; in contrast, it strongly increased [3H]TdR incorporation of PBL stimulated by CD2 pairs of mAb or by CD3 mAb linked to the plastic culture plates, when purified T cells were used, H90 mAb could efficiently induce them to proliferate after a primary signal of activation delivered via cross-linked CD3 or via CD2, an effect mediated by Il-2 synthesis and Il-2R expression. Thus, the effect of H90 mAb resembles the mitogenic effect of CD28 "9.3" mAb. However, several results show that CD28 and CD44 mediate different signals to the T cells: i) in contrast to CD28 mAb, CD44 mAb cannot complement the signal delivered by a soluble CD3 mAb, lectins, or PMA; ii) CD44 mAb, at the difference of CD28 mAb, cannot induce CD3+ thymocytes to proliferate in conjunction with a first signal provided via cross-linked CD3 or via CD2; iii) F(ab) fragments of H90 were efficient, whereas divalent fragments of CD29 9.3 mAb are required to produce activation signals; and iv) CD44 and CD28 mAb produce a very strong synergistic effect on T cell proliferation. These results fit with previous ones showing that endothelial cells can play the role of accessory cell in T cell activation and that a hierarchy of signaling can be delivered to T cells via CD3 and CD2.
Analysis of the interaction of peptide hen egg white lysozyme (34-45) with the I-Ak molecule.
Authors: Lambert L E , Unanue E R 
Published: December 2022

Abstract
We examined the structural characteristics of a peptide Ag that determine its ability to interact with class II-MHC molecules and TCR. The studies reported here focused on recognition of the hen egg white lysozyme (HEL) tryptic fragment HEL(34-45) by two I-Ak-restricted T cell hybridomas. HEL(34-45) bound to I-Ak created more than one antigenic specificity. Experiments with truncated peptides and alanine-substituted peptides indicated that two T cell hybrids either recognized distinct regions of the HEL(34-45) peptide, or different determinants generated by interaction of the peptide with I-Ak. Although we identified residues of HEL(34-45) that were critical to T cell recognition, no positions in the peptide were identified as I-Ak contact sites using single alanine substitutions. This suggests that more than one site or region of the peptide contributes to the binding to I-Ak. Finally, the murine lysozyme equivalent of 34-45 did not bind to I-Ak. Substitution of the corresponding murine lysozyme (self) residue at position 41 of HEL(34-45) abrogated I-Ak binding of the peptide.
Host resistance to cyclosporine induced syngeneic graft-versus-host disease. Requirement for two distinct lymphocyte subsets.
Authors: Fischer A C , Laulis M K , Horwitz L , Beschorner W E , Hess A 
Published: December 2022

Abstract
Cyclosporine is crucial for the prevention of organ allograft rejection and allogeneic graft-vs-host disease (GVHD). Despite its potent immunosuppressive activity, cyclosporine elicits a T cell-mediated autoimmune syndrome after autologous or syngeneic bone marrow transplantation, which has been termed syngeneic GVHD (SGVHD). Recent studies have shown that for disease manifestation, a cytoxan and radiation-sensitive T cell dependent host resistance mechanism must be eliminated, allowing the clonal expansion of autoreactive cells. This report characterizes the autoregulatory lymphocyte population, present in normal animals, capable of inhibiting the adoptive transfer of SGVHD. First, twice the number of unfractionated splenocytes from normal animals to those from autoimmune donors ensured complete inhibition of the adoptive transfer of immune reactivity. Second, the phenotype of this host resistance mechanism in normal splenocytes involves dual regulatory T cell subsets. A helper/inducer subset (W3/25+) must be cotransferred with a cytotoxic/suppressor subset (OX8+) in a ratio that approximates the normal ratio in normal unfractionated splenocytes in order to affect inhibition of the transfer of SGVHD. Moreover the specific inducer regulatory activity resides in the OX22-, W3/25+ subset of Th cells.
Identification of a widely distributed 90-kDa glycoprotein that is homologous to the Hermes-1 human lymphocyte homing receptor.
Authors: Pals S T , Hogervorst F , Keizer G D , Thepen T , Horst E , Figdor C C 
Published: December 2022

Abstract
Homing of recirculating lymphocytes from the blood into the lymphoid tissues is mediated by 90-kDa homing receptors on the lymphocyte cell surface, allowing selective binding to specialized endothelium lining high endothelial venules. This study describes two novel mAb, NKI-P1 and NKI-P2, directed against functional epitopes of a human lymphocyte homing receptor, gp90. Biochemical studies demonstrated that these antibodies recognize a 90-kDa glycoprotein which is similar to the Ag recognized by the mAb Hermes-1. This notion was confirmed by immunohistochemical studies showing identical reaction patterns. Furthermore, it was observed that NKI-P1 and NKI-P2 blocked adhesion of lymphocytes to high endothelial venules. Immunohistochemical, immunofluorescence, and immunoprecipitation studies revealed that gp90 is widely expressed on hemopoietic cells including lymphocytes, macrophages/dendritic cells, myeloid cells, and erythrocytes. The gp90 is also expressed on a number of nonhemopoietic cells such as endothelial cells, certain epithelial cells, and fibroblasts. In addition to its expression on normal cells, gp90 is present on a spectrum of tumor cell lines of lymphoid, monocytic, epithelial, glial, and melanocytic origin. In addition to the 90-kDa product, the antibodies immunoprecipitate several polypeptides in the range of 120 to 200 kDa. Interestingly, it was observed that certain mamma tumor cell-line cells lack the 90-kDa polypeptide indicating the heterogeneous expression of the molecules recognized by the antibodies. These results indicate that the 90-kDa glycoprotein homologues of the Hermes-1 human lymphocyte homing receptor are expressed on hemopoietic tissues as well as on a number of nonhemopoietic tissues and tumor cell lines. Although the function of these molecules in nonlymphoid cells is presently unknown, they might play a role in cell-cell or cell-matrix adhesion.
Inhibition of early murine hemopoietic progenitor cell proliferation after in vivo locoregional administration of transforming growth factor-beta 1.
Authors: Goey H , Keller J R , Back T , Longo D L , Ruscetti F W , Wiltrout R H 
Published: December 2022

Abstract
Transforming growth factor-beta 1 (TGF beta 1) has been shown in vitro to be a potent negative regulator of growth and differentiation of early hemopoietic progenitor cells, but not of more mature progenitors. However, little information is yet available regarding similar effects in vivo. We have developed an approach whereby TGF beta 1 can be administered locoregionally to the bone marrow via direct injection into the femoral artery. Our studies show that intrafemoral administration of a single bolus dose of TGF beta 1 potently inhibits the baseline and IL-3-driven proliferation of bone marrow cells. This inhibition is relatively selective for the earlier multipotential granulocyte, erythroid, megakaryocyte, and macrophage CFU progenitor cells since these are completely inhibited while the more differentiated CFU assayed in culture colonies are inhibited by about 50%. The inhibition of hemopoietic progenitor growth and differentiation is both time and dose dependent with the maximal effect on the marrow observed at 24 h with doses greater than or equal to 5 micrograms/mouse, and the effect is reversed at later times. A possible practical implication of these in vivo results could be the use of TGF beta 1 to protect stem cells in the bone marrow from the myelotoxic effects of chemotherapeutic drugs.