bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo.
Authors: Bukowski J F , Woda B A , Habu S , Okumura K , Welsh R M 
Published: December 2022

Abstract
The role of natural killer (NK) cells in the natural resistance of mice to infections by several viruses was examined. Mice were specifically depleted of NK cells by i.v. injection of rabbit antiserum to asialo GM1, a neutral glycosphingolipid present at high concentrations on the surface of NK cells. Control mice were left untreated or were injected with normal rabbit serum. Four to 6 hr later, these mice were infected with lymphocytic choriomeningitis virus (LCMV), mouse hepatitis virus (MHV), murine cytomegalovirus (MCMV), or vaccinia virus. The mice were sacrificed 3 days post-infection and assayed for virus in liver and spleen, spleen NK cell activity, and plasma interferon (IFN). All mice treated with anti-asialo GM1 antibody had drastically reduced NK cell-mediated lysis. Correlating with NK cell depletion, these mice had significantly higher (up to 500-fold) titers of MCMV, MHV, or vaccinia virus in their livers and spleens as compared to control mice. NK cell-depleted MCMV and MHV-infected mice had higher levels of plasma IFN than controls, correlating with the higher virus titers. These NK cell-depleted, virus-infected mice had more extensive hepatitis, assayed by the number of inflammatory foci in their livers, as compared to control virus-infected mice; these foci were also larger and contained more degenerating liver cells than those in control mice. In contrast to the results obtained with MHV, MCMV, and vaccinia virus, NK cell depletion had no effect on virus titers in the early stages of acute LCMV infection or during persistent LCMV infection. Mice depleted of NK cells had similar amounts of LCMV in their spleens and similar plasma IFN levels. Because this antibody to asialo GM1 does not impair other detectable immunologic mechanisms, these data support the hypothesis that NK cells act as a natural resistance mechanism to a number of virus infections, but suggest that their relative importance may vary from virus to virus.
Increase in NK cell number and turnover rate during acute viral infection.
Authors: Biron C A , Turgiss L R , Welsh R M 
Published: December 2022

Abstract
NK cell turnover and division during infection of mice with lymphocytic choriomeningitis virus (LCMV) was examined. Treatments with hydroxyurea (HU), a drug specific for cells synthesizing DNA, had no effect on control spleen NK cells, but significantly reduced NK cell-mediated lysis in LCMV-infected mice. When HU was administered at 9 and 2 hr before spleen cell harvest, the augmented lysis mediated by NK cells isolated from LCMV-infected mice was only 40% of that mediated by NK cells isolated from LCMV-infected untreated mice. Spleen cells that had been pulse-labeled with [3H]thymidine were used in a single cell assay with autoradiography to detect lysis mediated by blast cells. HU eliminated blast-NK cells; 34% of activated NK cell killing was mediated by blast cells, whereas less than 12% of the reduced NK cell activity after HU treatments was blast cell-mediated. The NK cells activated in vivo had lower densities than control NK cells. Although the total cell yields from control spleens and spleens on day 3 post-infection with LCMV were similar, low density Percoll gradient fractions from the day 3 spleen cell preparations contained three times as many cells as equivalent fractions from control populations. The same low density fractions were enriched in NK cell activity and in blast-NK cells. Activated spleen cell populations also contained increased numbers of large granular lymphocytes. These data indicate that NK cells have increased turnover rates during viral infection, that this increase in turnover is accompanied by NK cell division, and that this results in increases in the numbers of NK cells.
Demonstration of Aleutian disease virus-specific lymphocyte response in mink with progressive Aleutian disease: comparison of sapphire and pastel mink infected with different virus strains.
Authors: Race R E , Bloom M E , Coe J E 
Published: December 2022

Abstract
Lymphocyte blastogenesis was used to study the antiviral lymphocyte response of sapphire (Aleutian) and pastel (nonAleutian) mink inoculated with Pullman or Utah 1 Aleutian disease virus (ADV). Both mink genotypes developed a virus-specific response when inoculated with Utah 1 ADV. In contrast, after inoculation of Pullman ADV, sapphire mink had a positive virus-specific response, whereas pastel mink did not. Response occurred late after infection (8 wk) and correlated with the development of progressive Aleutian disease (AD). The response to keyhole limpet hemocyanin (KLH) and concanavalin A (Con A) was also determined. Most mink of either genotype, inoculated with either virus strain, maintained an anti-KLH response during disease. Most mink also responded to Con A, although some exhibited suppressed Con A response late in the disease course. These results indicated that mink develop an anti-ADV lymphocyte response during progressive AD and are not immunosuppressed with regard to other antigens or mitogens.
An allotype linked gene that is associated with a negative or very low anti-phosphorylcholine response (PC) phenotype in wild mice (CNV).
Authors: Lieberman R , D'Hoostelaere L A , Humphrey W , Nishinarita S , Potter M 
Published: December 2022

Abstract
In contrast to most inbred and wild mice, a population of wild mice recently isolated from a farm in Centreville, MD, and designated CNV produced no anti-phosphorylcholine (PC) antibodies (less than 1 microgram/ml) in response to immunization with the PC antigen Streptococcus pneumoniae (R36A) and gave 9 to 36 micrograms/ml anti-PC response to PC-KLH at 14 days after immunization. When another carbohydrate antigen, namely, bacterial levan, was used, CNV mice all gave high antibody titers. When CNV (PC-) mice were bred to inbred C.B20 (PC+) mice, 82% of the F1 and 76% of the F2 hybrids were surprisingly non-responders (PC-), which suggested that PC- gene(s) of CNV origin dominated the response to these antigens. The 18% PC+ phenotype in the F1 hybrids indicated possible heterozygosity of the PC genes controlling the PC- response in the CNV mice. Genetic studies on CNV mouse No. 378 supported this possibility. Analysis of the F2 data strongly suggest that two genes determined the PC- response, one of which was closely linked to the Igh-C allotype locus (chromosome 12). Hypothetically, we propose that CNV mice have two genes that cooperate but that sometimes act independently to express the PC- phenotype. Surprisingly, when F1 mice giving PC- phenotypes were back-crossed to C.B20, very few mice (18%) were PC-. This indicated that the PC- determining genes of CNV origin were not able to dominate immune responses in the presence of a larger number of C.B20 genes. This kind of expression may be regulated by other factors, such as clonotype competition and clonal dominance.
Xenoantisera against a murine T cell tumor product cross-react with immunoglobulin Fab determinants.
Authors: Mackel A M , Craddock G R , Warr G W , DeLuca D , Marchalonis J J 
Published: December 2022

Abstract
Some murine monoclonal T lymphoma cells express a surface component that reacts with chicken antisera produced against the Fab fragment of normal mouse IgG. In the present study, we use a solid phase immunoadsorbent consisting of affinity-purified chicken anti-Fab coupled to Sepharose to isolate a product produced by the in vitro T cell line, WEHI-7.1. The affinity-purified T cell surface molecule (IgT) migrated on SDS-PAGE as a single band of approximately 65,000 daltons. The object of these studies was to produce xenoantisera against the purified T cell product cross-reactive with Ig determinants and to characterize the antisera. Rabbits immunized with this purified molecule produced antibodies that reacted with Fab fragments of polyclonal mouse IgG and with the myeloma proteins MOPC-104E and MOPC-41, as detected by enzyme-linked immunosorbent assay (ELISA). This binding was eliminated by adsorption of the antisera with normal polyclonal IgG; however, adsorption with fetuin did not significantly affect the reactivity of the antisera. Radioimmune precipitation assays revealed that the rabbit anti-IgT bound to normal murine spleen and thymus cells; this reactivity was abrogated by adsorption with insolubilized polyclonal IgG. Competition radioimmunoassays demonstrated that detergent extracts of the thymus and the spleen contained material that inhibited the precipitation of MOPC-41; nonlymphoid cells lacked such material. The rabbit anti-IgT serum blocked the binding of antigen by normal T cells; adsorption of the antiserum with polyclonal IgG-Sepharose abrogated this blocking capacity. A solid phase immunoadsorbent prepared from the IgG fraction of the rabbit anti-IgT isolated a single component from formic acid-solubilized mouse thymus. This molecule had an approximate mass of 65,000 to 70,000 daltons. The anti-IgT serum isolated surface IgM and IgD from lactoperoxidase-catalyzed radioiodinated B cells. The anti-IgT serum detected IgM and IgG in mouse serum with the use of immunoelectrophoresis. The anti-IgT immunoadsorbent isolated several components from normal mouse serum, that, when analyzed by SDS-PAGE under reducing conditions, revealed bands corresponding to mu-, gamma-, and light chains as well as components that migrated between mu- and gamma-chains, and another component with an approximate mass of 45,000 daltons. Our results with antibodies to a purified T cell product indicate that a surface component of normal T cells and certain monoclonal T cell tumor lines is serologically related to the Fab fragment of serum Ig and is implicated in the binding of antigen.
Immunotherapy of a murine B cell tumor with antibodies and F(ab')2 fragments against idiotypic determinants of its cell surface IgM.
Authors: Perek Y , Hurwitz E , Burowski D , Haimovich J 
Published: December 2022

Abstract
Anti-idiotype antibodies against the IgM of the 38C-13 murine B lymphocyte cell line and F(ab')2 fragments derived from them were checked for their therapeutic effect against the killing of mice by 38C-13 cells. Both intact molecules and the F(ab')2 fragments were effective in delaying or preventing the killing of mice by 38C-13 tumors when used in large amounts and by the appropriate routes.
Induction of T cell responses in nonresponder mice by abolishing suppression with monoclonal antibodies recognizing A region-controlled, T cell-specific determinants.
Authors: Ikezawa Z , Nonaka M , Abe R , Tada T , Nagy Z A , Klein J 
Published: December 2022

Abstract
Mouse strains carrying the kappa allele at loci A beta, A alpha, E beta, and E alpha are nonresponders to lactate dehydrogenase B (LDHB) and to allotypic determinants of IgG2a myeloma proteins (for example, UPC10 used in this study). The nonresponsiveness to these antigens is caused by T suppressor (Ts) cells that prevent antigen-primed T helper (Th) cells from proliferating. We demonstrate here that monoclonal antibodies specific for an A region-controlled molecule selectively expressed on T cells (A-T) are capable of inducing anti-LDHB and anti-UPC10 responses of primed T cells from nonresponder strains. A monoclonal anti-J antibody that cross-reacts with the A-T molecule also induces responsiveness, whereas another J-specific antibody that lacks this cross-reactivity fails to do so. The mechanism of response induction is blocking of the interaction between the Ts cell or its factor (TsF) and the target of suppression, the antigen-specific Lyt-1+2- (Th) cell. The blocking occurs at the level of the Ts cell and the TsF. The data indicate that Ts cells and TsF carry a unique, A region-controlled molecule that is not only functionally analogous but also serologically similar to the J molecule.
Self recognition of accessory cell Ia determinants is required for the in vitro generation of hapten-specific cytotoxic T lymphocyte responses.
Authors: Kruisbeek A M , Andrysiak P M , Singer A 
Published: December 2022

Abstract
The present study has addressed the involvement of Ia determinants in the in vitro generation of antigen-specific cytotoxic T lymphocyte (CTL) responses. It demonstrated that the in vitro generation of TNP-specific CTL responses strictly requires responder T cell recognition of self-Ia determinants expressed by accessory cells, and that this recognition could be specifically inhibited by monoclonal anti-Ia-antibodies. The generation of TNP-specific CTL responses was unaffected by the presence of anti-I-A antibodies or the absence of accessory cells when cultures were performed in the presence of an exogenous source of T helper cell factors, Con A SN. Thus, these results indicate that T helper cell recognition of self-Ia determinants expressed by accessory cells is required for the generation of TNP-specific CTL responses. These results preclude the possibility that accessory cells perform only immunologically nonspecific roles in the generation of hapten-specific CTL, but instead demonstrate that accessory cells function in such responses as Ia-bearing antigen-presenting cells for the activation of self-Ia-specific T cells.
The cellular mechanism of maintenance of neonatally induced tolerance to H-2 class I antigens.
Authors: McCarthy S A , Bach F H 
Published: December 2022

Abstract
We used limiting dilution analysis protocols to investigate the mechanism by which in vitro cytotoxic T lymphocyte (CTL) hyporeactivity is maintained in adult mice that had been neonatally tolerized to major histocompatibility complex-encoded antigens. Class I molecules, presented on donor cells having an H-2 K or D region haplotype difference from recipients, readily induce tolerogen-specific CTL hyporeactivity. All attempts to identify any in vitro effects of active suppressive cells operative in the maintenance of this hyporeactivity have been unsuccessful. We conclude that this cytotoxic deficiency is the consequence of in vivo mediated clonal inactivation of the precursors of tolerogen-specific CTL. A presentation and evaluation of the assumptions inherent in this conclusion are made. In contrast to class I molecules, class II molecules, presented on donor cells having an H-2 I region haplotype difference from recipients, are unable to induce tolerogen-specific CTL hyporeactivity, even when injected neonatally at high doses. This inability of class II molecules to induce CTL tolerance parallels the considerable difficulty of inducing helper T lymphocyte tolerance to class II molecules.
Allergic contact dermatitis induced by intratracheal administration of hapten.
Authors: Stein-Streilein J 
Published: December 2022

Abstract
It is known that the skin is the natural route for induction of allergic contact dermatitis (ACD). Because the lung is another potential portal of entry for sensitizing chemicals, studies were performed to evaluate immune responses to haptens deposited in the lung. As a result, a new method for inducing ACD was developed. Intratracheal (IT) inoculation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) led to maximal ear swelling 24 hr after challenge on the ear with 2,4,6-trinitrochlorobenzene (TNCB) in carrier. This response was specific for immunizing hapten. Furthermore, it was equally possible to induce ACD by intratracheal inoculation of trinitrophenyl- (TNP) modified bronchoalveolar cells (BAC) or haptenated spleen cells. Adoptive transfer studies demonstrated that the hypersensitivity that resulted from IT inoculation of TNBS or TNP BAC could be transferred with cells. With a monoclonal anti-hamster Ia reagent, it was demonstrated that, like Langerhans cells, 80 to 90% of cells in the bronchial lavage fluid expressed Ia determinants on their membrane. These cells were morphologically indistinguishable from macrophages. Because an individual is capable of being sensitized when hapten is introduced by the pulmonary or epicutaneous routes, the possibility is raised that the alveolar macrophages in the lung possess a similar capability for antigen presentation of hapten in the induction of ACD as does the Langerhans cell.
Generation and characterization of monoclonal antibodies reactive with human B lymphocytes.
Authors: Mittler R S , Talle M A , Carpenter K , Rao P E , Goldstein G 
Published: December 2022

Abstract
Four novel monoclonal antibodies directed at determinants on human B lymphocytes were produced and characterized by flow cytometry using indirect immunofluorescence analysis. The antibodies, OKB1, OKB2, OKB4, and OKB7, define antigens not previously described on human B lymphocytes using B cell reactive monoclonal antibodies or standard B cell phenotypic markers. OKB4 [immunoglobulin M (IgM)] and OKB7 (IgG2a) were reactive with greater than 95% of all surface membrane immunoglobulin positive (Smlg+) lymphocytes and were restricted to the B cell lineage. OKB2 (IgG1) likewise reacted with greater than 95% of all Smlg+ lymphocytes; however, the antigen was also expressed on all granulocytes. In contrast to OKB2, OKB4, and OKB7, OKB1 reacted with a variable percentage of normal peripheral B cells (approximately 70 to 95%). Functional studies employing polyclonally activated B cells in a pokeweed mitogen (PWM) driven system and the reverse hemolytic plaque assay for the quantitation of Ig secreting plasma cells demonstrated that OKB1 and OKB2 inhibited the generation of plaque-forming cells (PFC) when added to cultures at day 0. OKB4 had a marginal inhibitory effect, whereas OKB7 consistently enhanced the PFC response. Immunoprecipitation studies with OKB1, OKB4, and OKB7 demonstrated that these antibodies precipitated antigens of approximately 168,000, 87,000, and 175,000 m.w., respectively. The OKB2 antigen is presently under study.
Selective inhibition of anti-nucleoside-specific antibody production by nucleoside-ricin A conjugate.
Authors: Morimoto C , Masuho Y , Borel Y , Steinberg A D , Schlossman S F 
Published: December 2022

Abstract
The effect of the preincubation of peripheral blood lymphocytes, from SLE patients, with nucleoside-ricin A conjugates on spontaneous A,G,C,T antibody production was examined. Enhanced spontaneous anti-nucleoside-specific antibody (anti-A,G,C,T antibody) production by SLE B cells was selectively inhibited by pretreatment in vitro with nucleosides conjugated to the ricin A chain. The selective suppression was demonstrated by the lack of suppression of the anti-DNP response or of polyclonal IgG production by pretreatment that did suppress anti-A,G,C,T production by the lymphocytes of eight patients with SLE. Furthermore, pretreatment of B cells, but not of T cells, with nucleoside-ricin A conjugates inhibited the A,G,C,T antibody response by these B cells. Thus, (A,G,C,T)-BGG-ricin A conjugates bind directly to the nucleoside-specific B cells via their antigen receptors. This demonstration of the selective elimination of B cells might have therapeutic applications in SLE.
Human bone marrow allograft recipients: production of, and responsiveness to, interleukin 2.
Authors: Warren H S , Atkinson K , Pembrey R G , Biggs J C 
Published: December 2022

Abstract
The production and utilization of interleukin 2 (IL 2) by peripheral blood mononuclear cells (PBMC) from 14 bone marrow allograft recipients was examined. PBMC from all patients were impaired in their ability to produce IL 2 when stimulated by phytohemagglutinin (PHA). On the average, the IL 2 activity produced by patients' PBMC was 8% of that from normal donors' PBMC. To examine the basis for this impaired T cell function in marrow recipients, the ability of a resting T lymphocyte population isolated from PBMC to respond to PHA and exogenously supplied IL 2 was analyzed. The proliferative response of resting T cells to PHA and IL 2, although low at early times post-transplant, reached near normal levels by 8 mo. Only two of 11 patients had normal numbers of precursor T cells that could respond. For all other patients the average number of precursor T cells was 10-fold lower than the average determined for normal donors. The impaired production of IL 2 by patients' PBMC may be due to this low precursor frequency. For some patients the rate and/or extent of clonal expansion of activated T cells appears to be greater than that of normal donors. The data suggest that the therapeutic application of IL 2 to such patients is unlikely to be successful in overcoming defects of T cell function before 8 mo post-marrow transplant.
Purified human monocyte subsets as effector cells in antibody-dependent cellular cytotoxicity (ADCC).
Authors: McCarley D L , Shah V O , Weiner R S 
Published: December 2022

Abstract
Human peripheral blood monocytes are heterogeneous with respect to their size and function. Two monocyte subsets were isolated by countercurrent centrifugal elutriation and were studied with respect to their ability to effect antibody-dependent cellular cytotoxicity (ADCC) and for the presence of Fc receptors on their surface. Both monocyte subsets display Fc surface receptors and are effectors of ADCC against sensitized human erythrocyte target cells. The demonstration of ADCC by monocyte effectors is dependent on their concentration in the incubation mixture. Dilution of monocytes below 10% by unlabeled and unsensitized erythrocytes or lymphocytes significantly suppresses ADCC, presumably by steric inhibition of effector and target contact.
The simultaneous antagonistic effects of a T cell hybridoma product on the growth and the maturation of activated lymphocytes.
Authors: Primi D 
Published: December 2022

Abstract
Lymphocyte maturation and growth are two antagonistic events; therefore, successful antibody synthesis accompanied by clonal expansion, as seen in most humoral immune responses, must be the result of a delicate quantitative balance between maturation and growth factors. On the basis of this hypothesis, it should be feasible to search for a T cell product that alters this equilibrium and favors either B cell growth or maturation. In an attempt to isolate T cell hybridomas producing these activities, we fused BW5147 thymoma cells with Con A-activated spleen cells. One of the hybridomas obtained constitutively produces a product (or products) that selectively inhibits mitogen-induced replication but not maturation of normal but not transformed B lymphocytes. More importantly, the same product(s) supports Ig synthesis but not growth of LPS blasts, which suggests that we are dealing with a B cell maturation factor. The effect of this supernatant can be completely abrogated by the B cell mitogen DxS. In addition, the proliferative response of B cells to this ligand is unaffected by the hybridoma product. The implications of our results for understanding the mechanism of B cell triggering are discussed.