bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased endogenous retroviral gene expression is a consequence of lymphocyte activation.
Authors: Ewert D L , Vainio O , Halpern M S 
Published: December 2022

Abstract
Plasma cells of line 151(5) chickens have been shown to express elevated levels of endogenous retroviral envelope glycoprotein (VEG), measured relative to levels expressed by both immature B cells and resting peripheral B lymphocytes. In this study we analyzed the relationship between peripheral blood lymphocyte (PBL) maturation and the level of VEG expression. A culture system was developed that would support maturation of pokeweed mitogen-activated peripheral B lymphocytes. As analyzed by cytofluorometry, both Ig+ and Ig- lymphoblasts present in the pokeweed mitogen-stimulated cultures expressed detectable levels of VEG in contrast to bursacytes and PBL. Similarly, Ig- blasts, which were present in concanavalin A-stimulated cultures of PBL and presumed to represent activated T cells, were also positive for the expression of VEG. Immature T cells, i.e., thymocytes, although negative by immunofluorescence analysis, expressed VEG at levels that were detectable by radioimmunochemical techniques. These results indicate that T cells as well as B cells constitutively express VEG, and that mitogenic activation of the resting lymphocyte induces an increase in VEG expression.
Recombination and mutation of class II histocompatibility genes in wild mice.
Authors: Wakeland E K , Darby B R 
Published: December 2022

Abstract
We have compared the tryptic peptide fingerprints of the A alpha, A beta, E alpha, and E beta subunits encoded by four wild-derived H-2 complexes expressing A molecules closely related to Ak. The A molecules encoded by these Ak-related mice have A alpha and A beta subunits that differ from A alpha k and A beta k by less than 10% of their tryptic peptides. Comparisons among the four wild-derived A molecules suggested that these contemporary A alpha and A beta alleles arose by sequential mutational events from common ancestor A alpha and A beta alleles. These results suggest that A alpha and A beta may co-evolve as an A beta A alpha gene duplex in wild mice. Tryptic peptide fingerprint comparisons of the E beta gene linked to these Ak-related A beta A alpha gene duplexes indicate that two encode E beta d-like subunits, whereas another encodes an E beta s-like subunit. These results strongly suggest that the A beta A alpha duplex and E beta recombine in wild mouse populations. The significantly different evolutionary patterns exhibited by the class II genes encoding A vs E molecules are discussed.
Cell surface expression of cytotoxic T lymphocyte-defined, AKR/Gross leukemia virus-associated tumor antigens by normal AKR.H-2b splenic B cells.
Authors: Green W R 
Published: December 2022

Abstract
We previously described a system in which H-2Kb-restricted C57BL/6 (B6) cytotoxic T lymphocytes (CTL) could be raised that were specific for tumors, such as the thymic lymphoma AKR.H-2b SL1, that were induced by endogenous AKR/Gross murine leukemia virus and that expressed the Gross cell surface antigen. In this study, certain normal lymphoid cells from AKR.H-2b mice were also found to express target antigens defined by such anti-AKR/Gross virus CTL. AKR.H-2b spleen, but surprisingly not thymus, cells stimulated the production of anti-AKR/Gross virus CTL when employed at either the in vivo priming phase or the in vitro restimulation phase of anti-viral CTL induction. This selective stimulation by spleen vs thymus cells was not dependent on the age of the mice over the range (3 to 28 wk) tested. Both AKR.H-2b spleen and thymus cells, however, were able to stimulate the generation of H-2-restricted B6 anti-AKR minor histocompatibility (H) antigen-specific CTL. Thus, AKR.H-2b spleen cells appeared to display the same sets (minor H and virus-associated) of cell surface antigens recognized by CTL as the AKR.H-2b SL1 tumor, whereas AKR.H-2b thymocytes were selectively missing the virus-associated target antigens, a situation analogous to that of cl. 18-5, a variant subclone of AKR.H-2b SL1 insusceptible to anti-AKR/Gross virus CTL. Like AKR.H-2b thymocytes, neither AKR spleen cells or thymocytes nor B6.GIX + thymocytes were able to stimulate the generation of anti-AKR/Gross virus CTL from primed B6 responder cell populations. In contrast, both T cell-enriched and B cell-enriched preparations derived from AKR.H-2b spleen cells were able to stimulate at the in vitro phase of induction, although B cell-enriched preparations were considerably more efficient. The discordant results obtained with AKR.H-2b spleen cells vs thymocytes were confirmed and extended in experiments in which these cells were employed as target cells to directly assess the cell surface expression of virus-associated, CTL-defined antigens. Thus, AKR.H-2b spleen cells, but not thymocytes, were recognized by anti-AKR/Gross virus CTL when fresh normal cells were tested as unlabeled competitive inhibitors, or when mitogen blasts were tested as labeled targets. Fresh or lipopolysaccharide-stimulated B cell-enriched spleen cells were as efficiently recognized as unseparated spleen cell preparations. Unexpectedly, fresh or Lens culinaris hemagglutinin-stimulated T cell-enriched spleen cell preparations, although susceptible to anti-minor H CTL, were almost as poor as targets for anti-viral CTL as were thymocytes. Together, these results demonstrate the H-2-restricted expression of CTL-defined, endogenous, AKR/Gross virus-associated target antigens by normal AKR.H-2b splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Differential expression of the invariant chain in mouse tumor cells: relationship to B lymphoid development.
Authors: Koch N , Harris A W 
Published: December 2022

Abstract
We have examined 25 cultured lines of mouse tumor cells for synthesis of the Ii, an Ia-associated polypeptide, by using an anti-Ii monoclonal antibody. Six of the T lymphomas tested did not produce detectable levels of Ii or of surface Ia antigens. Three B lymphomas and two plasmacytomas that express surface Ia antigens were found to synthesize the Ii. In addition, Ii was immunoprecipitated from two of five Ia- pre-B lymphomas, two of four Ia- plasmacytomas, two Ia- myeloid tumors, and two fibroblast cell lines including LM(TK-). Because Ia antigens have so far been found only on cells that also synthesize Ii, we suggest that the Ii is a marker of those cells that in certain states of development or activation express Ia antigens.
Inhibition of human natural killer cell reactivity by exogenous adenosine 5'-triphosphate.
Authors: Schmidt A , Ortaldo J R , Herberman R B 
Published: December 2022

Abstract
The presence of micromolar concentrations (5 to 100 microM) of adenosine 5'-triphosphate (ATP) in cytotoxicity assays of human natural killer (NK) cells with K562 targets resulted in marked inhibition of NK activity. NK activity of peripheral blood mononuclear cells (PBL) and of purified NK cells (i.e., large granular lymphocytes (LGL] were similarly sensitive to inhibition by ATP. The inhibitory activity was specific to ATP and was not demonstrated with GTP, UTP, CTP, or with other adenosine compounds. This inhibitory activity resulted from an effect of ATP on the effector cells and was not dependent on serum components. ATP did not inhibit binding of the LGL to target cells, and therefore the inhibition by ATP is presumed to be related to some post-recognition metabolic events. Some physiologic role in regulation of NK activity by ATP seems possible, because nonspecific phosphatases (bacterial alkaline phosphatase or human alkaline phosphatase) stimulated NK activity and partially reversed the ATP-induced inhibition of reactivity.
Interleukin 1-mediated induction of kappa-light chain synthesis and surface immunoglobulin expression on pre-B cells.
Authors: Giri J G , Kincade P W , Mizel S B 
Published: December 2022

Abstract
In this study we have examined the effect of interleukin 1 (IL 1) on the maturation of normal and neoplastic pre-B cells. We have found that IL 1 can enhance the in vitro functional maturation of surface immunoglobulin negative (sIg-) pre-B cells from normal bone marrow. In addition, IL 1 specifically induced sIg expression on an established pre-B cell line, 70Z/3. These effects of IL 1 were obtained with the same concentrations of IL 1 that are effective in assays for T cell proliferation and functional activation. Previous studies by other investigators have demonstrated that LPS can also induce the expression of sIg on 70Z/3 cells. The stimulatory effect of LPS was dependent on the stimulation of kappa-light chain synthesis, the synthesis of mu-chains being constitutive. Our results indicate that IL 1 may also enhance sIg expression via the induction of kappa-light chain synthesis. The stimulatory effect of IL 1 was not due to contaminating LPS in the IL 1 preparations, because removal of the IL 1 by using specific antibodies against IL 1 and fixed Staphylococcus aureus cells resulted in the disappearance of kappa-chain inducing activity. In addition to IL 1, a pH 2-sensitive mediator(s) present in concanavalin A (Con A)-stimulated spleen cell supernatants was also shown to induce kappa-chain synthesis and the appearance of sIg on 70Z/3 cells. Removal of IL 1 or the inhibition of any contaminating LPS activity with polymyxin B did not diminish the activity of the pH 2-sensitive Con A supernatant factor(s). On the basis of our findings, we have concluded that IL 1 may enhance antibody responses by not only increasing the number of helper T cells but also by stimulating the maturation of B cell precursors.
The functional capabilities of cells leaving the thymus.
Authors: Scollay R , Chen W F , Shortman K 
Published: December 2022

Abstract
There has been a controversy for many years over the functional status of cells that leave the thymus (thymus migrants) to populate the peripheral lymphoid organs. Are they immunoincompetent like cortical thymocytes and so probably derived from them, or are they functionally mature like medullary thymocytes? Until recently the techniques used to assess putative thymus migrants have been indirect, but it is now possible to measure the function of recent thymus migrants directly. We used intrathymic injection of a solution of fluorescein isothiocyanate to label thymocytes, and used electronic cell sorting to purify the fluorescent cells that accumulate in the periphery over the following 3 to 4 hr. The migrants have been enriched from an original frequency of about 1:1000 in lymph nodes and spleen, to greater than 98% purity. These cells have been compared with normal peripheral T cells for proliferative and cytotoxic precursor activity in a high cloning efficiency, lectin-induced, limit dilution culture system and in an allospecific limit dilution system. The frequency of precursors of proliferative lymphocytes and cytotoxic lymphocytes and the size of the clones produced is the same for recent migrants and peripheral T cells. Thus by the criteria of proliferation and cytotoxic responses to mitogens and generation of allospecific CTL, thymus migrants, a few hours after their emigration from the thymus, are fully immunocompetent; we therefore see no evidence of a post-thymic precursor-type cell that requires major maturation steps after leaving the thymus.
Spontaneous production of interferon-gamma in adult and newborn humans.
Authors: Martinez-Maza O , Andersson U , Andersson J , Britton S , De Ley M 
Published: December 2022

Abstract
By using a hemolytic plaque assay for IFN-gamma secretion by single cells, we found that one to three IFN-gamma secreting cells per 1 X 10(3) mononuclear cells were present in the blood from normal adult and newborn humans, without in vitro culture or stimulation by antigens or mitogens. The frequency of such cells was higher in newborns. These spontaneous IFN-gamma-secreting cells were predominantly T cells of the helper/inducer phenotype, as defined by treatment with monoclonal antibody and complement. By using indirect immunofluorescence staining, it was seen that 1% of blood mononuclear cells from adults and 3.5% from newborns contained cytoplasmic IFN-gamma. These cytoplasmic IFN-gamma-positive cells belonged to a heterogeneous population by morphology and by staining with monoclonal antibody. The majority of these cells were DR-positive T cells. We propose that these IFN-gamma-producing cells were activated in vivo, and that they possibly mediate antiviral or lymphokine activities.
Complement activation via the alternative pathway by purified Salmonella lipopolysaccharide is affected by its structure but not its O-antigen length.
Authors: Grossman N , Leive L 
Published: December 2022

Abstract
Salmonellae, the lipopolysaccharide of which differ in the chemical structure of their O-antigenic side chains, were previously shown to activate C3 at differential rates via the alternative pathway. We wanted to test whether lipopolysaccharide isolated from these strains yields identical results, and also the effect of the polysaccharide chain length, which varies from 0 to 40 or more repeating units in a single strain. Lipopolysaccharide was purified from the above strains, hydrolyzed (0.1 N NaOH, 56 degrees C, 30 min), and used to coat sheep erythrocytes to different densities, and C3 activation in C4-deficient guinea pig serum was measured. C3 activation was proportional to lipopolysaccharide density and time, and the relative rates and extents of activation by this bacteria-free system were the same as for the original bacteria. Activation was reduced 10 to 15% when the serum was preabsorbed with strains either containing or lacking O-antigen side chain, suggesting augmentation by antibody; however, even after multiple absorptions, activation varied with O-antigen structure as expected. This differential activation was not due to differences in the average length of the O-antigenic polysaccharide chains, because the size was similar for all three lipopolysaccharides. Moreover, the extent of activation by lipopolysaccharide that had been fractionated on a column of Sephadex G-200 was independent of the polysaccharide chain length for lengths greater than 3 repeating units. The results prove that C3 activation by lipopolysaccharide via the alternative pathway is sensitive to slight variations in the chemical structure, but not to large variations in length of the O-antigen polysaccharide side chain of lipopolysaccharide.
Generation of memory cell-mediated immune responses after secondary infection of mice with pichinde virus.
Authors: Walker C M , Rawls W E , Rosenthal K L 
Published: December 2022

Abstract
Pichinde virus (PV), a member of the arenavirus group, was found to elicit strong cell-mediated immune responses in various strains of mice. After primary i.v. inoculation, augmentation of natural killer (NK) cell activity occurred and peaked 3 to 4 days after infection. The NK response was followed by a second peak of cytotoxic activity that was found to be H-2 restricted, virus specific, and mediated by Thy-1.2+, Lyt-2.2+ lymphocytes. This cytotoxic T lymphocyte (CTL) response peaked 7 days post infection. Neutralizing antibodies were not detectable after PV infection of the mice. In light of this, we investigated the generation and kinetics of secondary cell-mediated immune responses after reinjection of homologous virus in vivo. Slight but significant augmentation of NK activity was observed 1 day after secondary virus challenge. As in the primary response, effectors of this NK activity rapidly became sensitive to anti-Thy-1.2 and complement treatment. NK activity rapidly returned to background levels and was followed by an anamnestic CTL response that peaked 4 days after reinjection of the virus. Thus, cell-mediated immune responses appeared more rapidly after secondary challenge in vivo, and the temporal relationship between NK and CTL generation was maintained. Both secondary NK and CTL responses were generated in mice that had been pretreated with cyclophosphamide (CY), suggesting that memory cell-mediated immune responses can be reactivated in vivo without undergoing cell division. In contrast, treatment with CY before primary infection delayed the appearance of virus-induced NK activity and abrogated the generation of H-2-restricted virus-specific CTL. Rechallenge of these CY-treated NK-primed mice resulted in the rapid generation of a secondary NK response that was not followed by either a primary or secondary CTL response. The data suggest that cells mediating a nonspecific effector function may possess specific memory. We discuss our results with respect to possible NK-CTL relationships.
Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity.
Authors: de Vries J E , Spits H 
Published: December 2022

Abstract
Activation of peripheral blood lymphocytes (PBL) from a melanoma patient either in secondary MLC in which EBV-transformed B cells from the cell line JY were used as stimulator cells, or by co-cultivation with the autologous melanoma cells in a mixed leukocyte tumor cell culture (MLTC) resulted in the generation of cytotoxic activity against the autologous melanoma (O-mel) cells. From these activated bulk cultures four cloned cytotoxic T lymphocyte (CTL) lines were isolated. The CTL clone O-1 (T3+, T4+, T8-, OKM-1-, HNK-, and HLA-DR+), and O-36 (T3+, T4-, T8+, OKM-, HNK-, and HLA-DR+) were obtained from MLC, whereas the CTLC clones O-C7 (T3+, T4+, T8-, OKM-1-, HNK-, and HLA-DR+) and O-D5 (T3+, T4-, T8+, OKM-1-, HNK, and HLA-DR+) were isolated from autologous MLTC. All four CTL clones were strongly cytotoxic for O-mel cells but failed to lyse autologous fibroblasts and autologous T lymphoblasts. Moreover, the CTL clones lacked NK activity as measured against K562 and Daudi cells. Panel studies indicated that the CTL clones also killed approximately 50% of the allogeneic melanoma cells preferentially, whereas the corresponding T lymphoblasts were not lysed. Monoclonal antibodies against class I (W6/32) and class II (279) MHC antigens failed to block the reactivity of the CTL clones against O-mel and allogeneic melanoma cells, indicating that a proportion of human melanoma cells share determinants that are different from HLA antigens and that are recognized by CTL clones. In contrast to the CTL clones isolated from MLTC, the clones obtained from MLC also lysed JY cells, which initially were used as stimulator cells. The reactivity of O-36 against JY could be inhibited with W6/32, demonstrating that this reactivity was directed against class I MHC antigens. These results suggest that the lysis of O-mel and JY cells by O-36 has to be attributed to two independent specificities of this CTL clone. The specificity of the other cross-reactive CTL clone (O-1) could not be determined. The notion that individual CTL clones can have two specificities was supported by the following observations. The cytotoxic reactivity of both O-1 (T4+) and O-36 (T8+) against JY was blocked by monoclonal antibodies directed against T3 and human LFA-1, and against T3, T8, and human LFA-1, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
T cells from naive mice suppress the in vitro cytotoxic response against endogenous Gross virus-induced tumor cells.
Authors: Tilkin A F , Gomard E , Begue B , Levy J P 
Published: December 2022

Abstract
Syngeneic normal lymphoid cells added in co-culture of immune lymphocytes and tumor cells reveal a suppressive activity inhibiting the generation of cytolytic T lymphocytes. The suppression was specific for the response directed against endogenous virus-induced or x-ray-induced tumor cells expressing endogenous C type virus antigens. Thymocytes, spleen cells, or lymph node cells from naive mice were able to express this suppressive activity. The same cells displayed no suppressive activity on killer cells directed against exogenous C type virus-induced tumor cells. The suppressor cells were Thy-1+, Lyt-1- 2+. Our results strongly suggested that the spontaneous suppressor cells exert their activity by interacting with an early step on the CTL response, probably at the level of the helper T cell function. The suppressive activity was mediated by soluble factor(s) that were antigen specific and possibly H-2 restricted. The possible implications of these spontaneous suppressor T lymphocytes in the development of endogenous virus-induced tumors and their possible implications in tolerance to self antigens are discussed.
Induction of specific unresponsiveness to heart allografts in mongrel dogs treated with total lymphoid irradiation and antithymocyte globulin.
Authors: Strober S , Modry D L , Hoppe R T , Pennock J L , Bieber C P , Holm B I , Jamieson S W , Stinson E B , Schroder J , Suomalainen H 
Published: December 2022

Abstract
The survival of heterotopic heart allografts was determined in mongrel dogs treated with total lymphoid irradiation (TLI) alone or in combination with other immunosuppressive agents. TLI alone (total dose, 1800 rad) minimally prolonged graft survival as compared with untreated controls. However, marked synergy was observed when TLI was combined with a 10-day post-transplant course of rabbit anti-dog thymocyte globulin (ATG). Approximately 40% of recipients given TLI and ATG showed specific unresponsiveness, as judged by the lack of rejection on serial biopsies for more than 1 yr and the prompt rejection of third party hearts. The addition of post-transplant azathioprine (90 to 180 days) to the TLI and ATG regimen increased the mortality of recipients and reduced the fraction of dogs showing specific unresponsiveness. Infusion of donor bone marrow cells at the time of heart transplantation failed to induce specific unresponsiveness in recipients given TLI alone or TLI in combination with post-transplant methotrexate, cyclosporine A, or ATG. The results indicate that the combination of TLI and a brief course of ATG without marrow transplantation was the most effective regimen for the induction of specific unresponsiveness in mongrel dogs.
Suppression of pokeweed mitogen-stimulated immunoglobulin production in patients with rheumatoid arthritis after treatment with total lymphoid irradiation.
Authors: Kotzin B L , Strober S , Kansas G S , Terrell C P , Engleman E G 
Published: December 2022

Abstract
Patients with intractable rheumatoid arthritis (RA) were treated with total lymphoid irradiation (TLI, 2000 rad). We previously reported long-lasting clinical improvement in this group associated with a persistent decrease in circulating Leu-3 (helper subset) T cells and marked impairment of in vitro lymphocyte function. In the present experiments, we studied the mechanisms underlying the decrease in pokeweed mitogen stimulated immunoglobulin (Ig) secretion observed after TLI. Peripheral blood mononuclear cells (PBL) from TLI-treated patients produced 10-fold less Ig (both IgM and IgG) in response to pokeweed mitogen than before radiotherapy. This decrease in Ig production was associated with the presence of suppressor cells in co-culture studies. By using responder cells obtained from normal individuals (allogeneic system), PBL from eight of 12 patients after TLI suppressed Ig synthesis by more than 50%. In contrast, PBL from the same patients before TLI failed to suppress Ig synthesis. Suppression by post-TLI PBL was also demonstrated in an autologous system by using responder cells cryopreserved before TLI. Again, only cells obtained after TLI were suppressive in four of seven patients. PBL with suppressive activity contained suppressor T cells, and the latter cells bore the Leu-2 surface antigen. In 50% of the patients studied, suppressor cells were also found in the non-T fraction and were adherent to plastic. Interestingly, the Leu-2+ cells from TLI-treated patients were no more potent on a cell per cell basis than purified Leu-2+ cells obtained before TLI. Additional experiments suggested that the suppression mediated by T cells after TLI is related to the increased ratio of Leu-2 to Leu-3 cells observed after radiotherapy.