bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating lymphocyte subpopulations in pregnancy: a longitudinal study.
Authors: Tallon D F , Corcoran D J , O'Dwyer E M , Greally J F 
Published: December 2022

Abstract
Peripheral blood lymphocyte subpopulations were studied sequentially during the gestation and the postpartum period of 84 obstetrically normal women. Both the percentage and absolute numbers of total peripheral blood lymphocytes decreased in the second and third trimester. Although there was a further decrease in percentage numbers 1 wk postpartum, the absolute numbers returned to normal. Absolute numbers of OKT3+ and of OKT4+ cells decreased in the second and third trimesters; OKT8+ cells decreased in the third trimester only. Absolute numbers of all T cells returned to normal postpartum. The absolute numbers of B lymphocytes, while showing no consistent pattern, decreased significantly in the third trimester and in the second postpartum period; however, the percentage values of all lymphocyte subpopulations did not alter during or after pregnancy. The data do not support the concept that a numerical imbalance in the T cell subpopulations has a causative role in the immunodeficiency of pregnancy.
Immunological studies of aging. IX. Impaired proliferation of T lymphocytes detected in elderly humans by flow cytometry.
Authors: Staiano-Coico L , Darzynkiewicz Z , Melamed M R , Weksler M E 
Published: December 2022

Abstract
Lymphocytes from humans over the age of 65 incorporate approximately 50% less tritiated thymidine than do lymphocytes from young donors when cultured with phytohemagglutinin. Because lymphocytes from elderly humans are more sensitive to cell cycle arrest induced by tritiated thymidine, it was impossible to determine to what extent impaired thymidine incorporation reflected a defect in proliferation or the increased sensitivity to the radioactive isotope. Flow cytometry was used to measure the proliferative response of T cells from young and old donors in culture with PHA. It was found that 25 percent fewer lymphocytes from old as compared to young humans enter the G1 or complete the S phase of the cell cycle. However, the rate of progression through the cell cycle by activated cells from young and old humans is comparable. Thus, flow cytometry suggested that the difference in thymidine incorporation by lymphocytes from old and young donors is attributable equally to a proliferative defect and to cell cycle arrest induced by tritiated thymidine. This conclusion was supported by the fact that the relative impairment of thymidine incorporation by lymphocytes from old donors was only one-half as great when a 20-min instead of a 24-hr pulse of tritiated thymidine was used.
Functional status of cells from lymphoid and myeloid tissues in mice with severe combined immunodeficiency disease.
Authors: Dorshkind K , Keller G M , Phillips R A , Miller R G , Bosma G C , O'Toole M , Bosma M J 
Published: December 2022

Abstract
Cells from mice with severe combined immunodeficiency disease (SCID) were tested in assays that measure myeloid and lymphoid function. Results showed that C.B-17 scid and their normal counterparts (C.B-17) have similar levels of spleen colony-forming units. The frequency of in vitro myeloid colony-forming units in C.B-17 scid spleen is elevated, but the absolute number of colony-forming units in C.B-17 scid and C.B-17 spleen is similar. The absolute number of bone marrow colony-forming units in C.B-17 scid and C.B-17 mice is comparable. Cells from C.B-17 scid spleen are consistently negative in all tests of B and T cell function. C.B-17 scid splenocytes fail to proliferate in response to T and B cell mitogens or to allogeneic lymphocytes in a one-way MLR; C.B-17 scid cells do serve as stimulators in MLR. B lymphocyte colony-forming units are absent, as are cytotoxic lymphocyte precursors and cells that can generate T cell colonies with cytotoxic progenitors. The microenvironment of the C.B-17 scid mouse is conducive to lymphocyte differentiation, because functional B and T cells are easily detectable in mice reconstituted with normal bone marrow cells. The results of this study indicate that scid specifically impairs the differentiation of stem cells into mature lymphocytes; myeloid cell differentiation is not affected.
Genetic analysis of susceptibility to Theiler's virus-induced demyelinating disease in mice.
Authors: Lipton H L , Melvold R 
Published: December 2022

Abstract
Genetic control of resistance and susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice was examined. Mice derived from various crosses between susceptible SJL (S) and resistant C57BL/6 (B6) strains allowed determination of the relative susceptibility contributed by H-2 and non-H-2 genes, as well as allowing segregation of H-2 linked genes. Six of 39 B6SF1 hybrid progeny developed disease, suggesting several possibilities--resistance is dominant and susceptibility recessive but with incomplete penetrance, the incidence of disease is dose dependent and is dictated by the number of "susceptible/resistant" alleles present at one or more loci, or some combination of the two. Data involving the progeny from the B6SF1 hybrids mated to the S parental strain indicated the involvement of more than one locus. The strong correlation between the number of H-2s haplotypes and the incidence of demyelinating disease suggested that at least one of the genes was linked to the H-2 complex; however, other independently segregating (unlinked) loci strongly affected the disease incidence among H-2 identical animals. A gene or genes from the S background was also associated with enhanced virus growth or diminished virus clearance in the central nervous system (CNS). Overall, the observations support a gene dosage model for susceptibility that relates disease incidence to the total number of S alleles at both H-2 and non-H-2 loci.
Acetylated diamines inhibit endotoxin-induced lymphocyte activation.
Authors: Ryan J L , Bondy P K , Gobran L , Canellakis Z N 
Published: December 2022

Abstract
Fully acetylated diamines hexamethylenebisacetamide (HMBA) and diacetylputrescine (tetramethylenebisacetamide, TMBA) cause inhibition of murine B lymphocyte activation in the absence of ruminant serum. Mitogenesis induced by LPS, LAP, and 8-BrcGMP was profoundly inhibited in the presence of 3 mM HMBA and TMBA. PHA-stimulated thymidine uptake was not affected. Higher levels of the acetylated polyamines were toxic to lymphocytes. Immunoglobulin secretion by LPS-stimulated spleen cells was inhibited in similar fashion. This inhibition requires the early addition of the polyamines and does not appear to be associated with direct inhibition of DNA synthesis. These data support the hypothesis that polyamines represent immunomodulatory agents and suggest that acetylated derivatives of polyamines may also have activity in regulating B lymphocyte activation.
Functional studies on the secreted form of human C4 (C4s), two incompletely processed two-subunit C4 molecules (beta - alpha + gamma and beta + alpha - gamma), and pro-C4.
Authors: Chan A C , Atkinson J P 
Published: December 2022

Abstract
The functional properties of the secreted form of C4 (C4s), which has a Mr approximately 5000 greater than the predominant C4 molecule found in plasma (C4p), two incompletely processed two-chain C4 molecules (beta - alpha + gamma and beta + alpha - gamma), and the extracellular C4 precursor (designated pro-C4(E)] were evaluated. All four molecules are secreted in parallel by a human hepatoma-derived cell line (Hep G2). Secretion of hemolytically active C4 is linear up to approximately 12 hr, peaks at 24 hr, and then progressively decreases over the next 48 hr. This loss of C4s functional activity parallels the proteolytic conversion of C4s to C4bs. To compare the hemolytic efficiencies of C4s and C4p, a solid-phase competitive radioimmunoassay was developed to permit measurement of the small quantities of C4 antigen in these cultures. The hemolytic efficiencies of C4s and C4p were similar. These results indicate that extracellular processing of C4s to C4p does not modulate the hemolytic activity of the molecule. Consistent with their ability to bind methylamine, both the alpha s-chain and the alpha - gamma subunit undergo denaturation-induced autolysis. The extracellular and intracellular pro-C4 molecules are also sensitive to autolytic cleavage. Interestingly, the beta - alpha subunit is resistant to autolysis. In experiments in which C4s and C4p were cleaved by C1-s to C4bs, C4(beta - alpha + gamma), C4(beta + alpha - gamma), and pro-C4(E) were resistant to C1-s cleavage and thus hemolytically inactive relative to C4s. These data indicate that processing of C4 to a three-chain structure is required to provide the proper conformation for efficient activation by C1.
IgE immune complexes induce immediate and prolonged release of leukotriene C4 (LTC4) from rat alveolar macrophages.
Authors: Rankin J A , Hitchcock M , Merrill W W , Huang S S , Brashler J R , Bach M K , Askenase P W 
Published: December 2022

Abstract
Alveolar macrophages obtained by lung lavage from rats were incubated with monoclonal mouse anti-DNP IgE and specific antigen (DNP-HSA) and were found to release a slow reacting substance (SRS), which was characterized by high performance liquid chromatography as leukotriene C4 (LTC)4. Alveolar macrophages incubated with 1 microM A23187 (calcium ionophore) released similar amounts of SRS (6.0 +/- 2.2 and 5.7 +/- 3.7 X 10(-10) mol of LTC4 per 5 X 10(6) alveolar macrophages, respectively). The optimal conditions and mechanism of LTC release by IgE and antigen were examined. LTC4 release was maximal when freshly retrieved alveolar macrophages were incubated for 20 min with 10 micrograms/ml IgE and then for 20 min with 100 ng/ml antigen or for 20 min with IgE and antigen that had been preincubated together for 30 min at room temperature. In addition, LTC4 release was maximal when cells were challenged with IgE and antigen in a protein-free balanced salt solution and when the cells were tumbled to prevent adherence. Dose response experiments revealed that macrophages released LTC4 when stimulated with as little as 10 ng IgE and 100 ng DNP-HSA. Alveolar macrophages did not release LTC when challenged with IgE or DNP-HSA alone. Activation of LTC4 release by IgE and antigen was rapid in onset (2.5 to 5 min), and washing to remove fluid phase IgE and antigen revealed that once activated, alveolar macrophages were capable of prolonged and continuous release of LTC4. Peritoneal lavage cells stimulated with IgE and antigen did not release SRS but could release SRS when incubated with A23187 (5.7 +/- 1.3 X 10(-10) mol LTC4/5 X 10(6) macrophages). A large variability existed between individual rats in the ability of their alveolar macrophages to be activated by IgE and antigen to release LTC4. DNP-HSA labeled with 125I was used to show formation of immune complexes of IgE and antigen when IgE and antigen were incubated together before macrophage challenge. IgE immune complexes containing as little as 2 ng of antigen elicited the release of LTC4 from alveolar macrophages. These data indicate that rat alveolar macrophages release primarily LTC4 when challenged with IgE immune complexes, and that the alveolar macrophage may differ in this respect from peritoneal macrophages that do not release detectable quantities of LTC4 when challenged under identical conditions.
Suppression of human lymphocyte responses by oral spirochetes: a monocyte-dependent phenomenon.
Authors: Shenker B J , Listgarten M A , Taichman N S 
Published: December 2022

Abstract
Spirochetes have been implicated in the pathogenesis of several human infections including syphilis, yaws, Lyme disease, and periodontal diseases. We examined soluble sonic extracts of oral spirochetes (Treponema denticola and T. vincentii) for their ability to alter human lymphocyte function. These organisms were isolated from subgingival plaque of patients with periodontitis. We found that sonicates of several but not all strains of T. denticola caused a dose-dependent inhibition of human lymphocyte responsiveness to Con A, PHA, PWM, and the recall antigen SKSD. Suppression involved alterations in DNA, RNA, and protein synthesis; there was no effect on cell viability. In contrast, sonicates of T. vincentii (medium-sized spirochetes) had no demonstrable effects on lymphocyte activation. The suppressive factor derived from T. denticola is heat-labile with a m.w. of approximately 100,000. To achieve maximal suppression, sonicates had to be added during the first 24 hr of incubation; there was no inhibition observed when added at 48 or 72 hr (along with 3H-TdR). Suppression was dependent on the presence of adherent monocytes; removal of these cells prevented spirochete-induced suppression of lymphocyte proliferation. Furthermore, the combination of indomethacin and catalase were able to reverse (or prevent) the inhibitory effects of the spirochete extracts, demonstrating a requirement for both prostaglandins and hydrogen peroxide. The potential role of such suppressive factors in periodontal disease is discussed.
Cutaneous leishmaniasis in anti-IgM-treated mice: enhanced resistance due to functional depletion of a B cell-dependent T cell involved in the suppressor pathway.
Authors: Sacks D L , Scott P A , Asofsky R , Sher F A 
Published: December 2022

Abstract
The contribution of B cells and antibodies to either the resistance or susceptibility to cutaneous leishmaniasis has been investigated in mouse strains rendered B cell-deficient by treatment with anti-mouse IgM antisera from birth (mu-suppressed). These studies confirm that immunity to cutaneous disease in a normally resistant mouse strain (C3H/HeJ) is independent of antibody, but that B cells and/or antibodies are required for the evolution of suppressed DTH and the consequent disease susceptibility of BALB/c mice. Anti-IgM-treated BALB/c mice, which lacked detectable anti-leishmanial antibodies during the course of infection, displayed a sustained DTH response to leishmanial antigen and were able to control their cutaneous lesions. The enhanced resistance of mu-suppressed mice could be completely abrogated by transfer of suppressor T cells from infected control animals into mu-suppressed mice before their infection. Thus the suppressor T cells, which are generated during leishmanial infection in BALB/c mice, can effect suppression in the absence of antibody. Evidence that B cells or antibodies are required for the generation of suppressor T cells was demonstrated by using BALB/c mice in which suppressor T cells fail to be generated during infection as a result of prior sublethal irradiation. Splenic T cells from normal mice could overcome the resistance conferred by sublethal irradiation, whereas splenic T cells from mu-suppressed mice could not. Thus the enhanced resistance of mu-suppressed BALB/c mice appears to be a consequence of their lack of functional expression of a B cell-dependent T cell critical to the suppressor pathway.
Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus.
Authors: Gervais F , Stevenson M , Skamene E 
Published: December 2022

Abstract
The control mechanisms responsible for the innate resistance of C57BL/6J (B) mice and for the innate susceptibility of A/J (A) mice to infection with Listeria monocytogenes were studied by typing the recombinant inbred (RI) strains derived from these two progenitors for the trait of Listeria resistance/susceptibility. The strain distribution pattern (SDP) of this trait obtained in the 13 AXB/BXA RI strains studied suggests that an allelic difference at a major locus (Lr-1) is responsible for the trait of resistance/susceptibility to Listeria. In addition, another putative gene (Lr-2) unlinked to Lr-1 is postulated to control the level of bacterial load within the group of susceptible strains. The SDP of A and B alleles at the Lr-1 locus was fully concordant with that observed for the Hc locus (controlling the level of the C5 component of complement). This suggests that the genetic susceptibility of A strains of mice to Listeria infection is either directly due to or related to the C5 deficiency found in that strain. This conclusion is enhanced by the observation of a significant protection of A mice from listeriosis by the infusion of C5-rich serum. A survey of RI strains for the magnitude of PMN and macrophage inflammatory responses showed that the expression of both traits co-segregated and that the C5 deficiency was the major factor responsible for the defective inflammatory response of A strain mice. We conclude that a defect in the phagocyte inflammatory responses caused by C5 deficiency is the major reason for the extreme susceptibility of A mice to Listeria.
Tumor radioimmunolocation: differential antibody retention by antigenic normal tissue and tumor.
Authors: Ballou B , Jaffe R , Taylor R J , Solter D , Hakala T R 
Published: December 2022

Abstract
On the assumption that a high specificity would be required for in vivo tumor location and drug targeting, much labor has been expended to produce monoclonal antibodies directed to antigens found primarily on tumors. However, for at least one tumor-associated antigen, stage-specific embryonic antigen 1 (SSEA-1), the concentration of the target antigen need not be higher in the tumor than that found in normal tissues for successful use of the corresponding monoclonal antibody in in vivo tumor location; rather, accessibility and antibody metabolism are more important.
The systemic administration of purified interleukin 2 enhances the ability of sensitized murine lymphocytes to cure a disseminated syngeneic lymphoma.
Authors: Donohue J H , Rosenstein M , Chang A E , Lotze M T , Robb R J , Rosenberg S A 
Published: December 2022

Abstract
Significant serum titers of interleukin 2 (IL 2) can be maintained in mice for 12 h after i.p. injection in a 15% gelatin solution. We have tested the ability of IL 2 administered systemically in this fashion to enhance the therapeutic effect of adoptively transferred specifically sensitized lymphoid cells that were expanded in IL 2. Mice with established local and disseminated FBL-3 lymphoma, induced by intrafootpad injection of 10(7) cells after 500 rad total body irradiation, were treated with a combination of i.v. injected murine splenocytes and either murine supernatants containing IL 2 or pure human IL 2 in gelatin. Splenocytes from immune mice were resensitized to irradiated tumor in vitro and were expanded for 7 days in lectin-free IL 2 supernatants. Treatment with these murine splenocytes administered with murine IL 2 supernatants prolonged mean survival to 33.6 days compared with mean survival times of 16.9 days (p less than 0.001) and 23.4 days (p = 0.007) for mice treated with IL 2 alone or splenocytes alone. Human IL 2, purified to homogeneity from the Jurkat cell line, was also capable of improving the therapeutic efficacy of transferred cells in mice. Mean survival was significantly prolonged to 32.1 days when cells and purified human IL 2 were administered, whereas mean survival times of 18.1 days (p = less than 0.001) and 21.5 (p = less than 0.001) were seen for mice treated with IL 2 alone or expanded immune cells alone. Cure rates in this model were also significantly enhanced with the combined treatment of IL 2 and expanded immune cells. Combined immunotherapy utilizing IL 2 and immune cells was thus significantly better than either component used alone. The systemic administration of IL 2 in conjunction with sensitized expanded lymphoid cells may be a useful approach to the immunotherapy of other murine and human tumors.
LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation.
Authors: Krensky A M , Robbins E , Springer T A , Burakoff S J 
Published: December 2022

Abstract
Three cell surface antigens associated with the CTL-target cell interaction were previously identified by generation of mAb against OKT4+, HLA-DR-specific CTL, and selection for inhibition of cytolysis in a 51Cr-release assay. In this report, we showed that these mAb inhibit cytolysis by blocking CTL-target cell conjugate formation. It appears that LFA-1, LFA-2, and LFA-3 are cell surface structures involved in strengthening effector-target adhesion that accompanies antigen-specific recognition.
Generation of the alloreactive T cell repertoire: K region homology between H-2b T cell precursors and T cell maturation environment is required for the generation of the Kbm6-specific cytotoxic T cell repertoire.
Authors: Gress R E , Hodes R J 
Published: December 2022

Abstract
The influence of T cell genotype and T cell maturation environment on the generation of the T cell alloreactive repertoire was evaluated in the H-2b cytotoxic T lymphocyte response to Kb mutant determinants expressed by the strain B6-H-2bm6. Specifically, by constructing radiation bone marrow chimeras with B6 or B10 (H-2b) donor cells and B10.BR, B10.A(4R), B10.MBR, and B6.C-H-2bm1 irradiated mice as recipients, it was possible to investigate the major histocompatibility complex (MHC)-encoded gene products of the host environment required for the generation of a bm6-specific H-2b CTL response. The results of such experiments confirmed the previous finding that the alloreactive T cell repertoire is influenced both by T cell MHC genotype and by the MHC gene products of the T cell maturation environment. In addition, the results of the present study further demonstrated that in the chimeric donor and host genetic combinations used, it was both necessary and sufficient that there be a homology of K region-encoded determinants for the generation of a bm6-specific CTL response. Experiments utilizing a mixed responder population of unresponsive B6----B10.D2 spleen cells and responsive Lyt-2 congenic B6.Lyt-2.1 spleen cell suggested that the cellular defect(s) underlying the unresponsiveness of the chimeric cells to bm6-encoded determinants was at the level of the CTL precursor. Together, these findings indicate that an interaction of the K region-encoded gene products of the T cell and its maturation environment play a critical role in the generation of the CTL repertoire specific for bm6 mutant determinants. We discuss here the possibility that this interaction may reflect a requirement that T cells recognize such mutant allodeterminants in association with self restriction elements present on the same mutant K region-encoded molecule.
Qa-like genes defined by CTL analysis of B10.W lines.
Authors: Vucak I , Juretić A , Vidović D , Nagy Z A , Klein J 
Published: December 2022

Abstract
Twelve responder-stimulator combinations of mouse B10.W strains identical at K, D, and class II loci were tested for the generation of cytolytic T lymphocytes (CTL). No primary CTL could be obtained in any of the combinations but in nine combinations CTL were generated after priming in vivo. Six of these CTL are described. They define five antigenic determinants expressed exclusively in a small group of B10.W lines. The determinants appear to be part of the same system that resembles the Qa system originally defined in classic inbred strains. This resemblance rests on the observation that in vivo priming is necessary for the generation of the CTL, and that the CTL are not restricted in their reactivity by known H-2 loci. At least some of the determinants, however, appear to be controlled by a locus (or loci) associated with the K-rather than the D-end of the H-2 complex. Furthermore, some of the CTL directed against these Qa-like determinants cross-react with a molecule controlled by the K locus.