bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in the migration of B and T lymphocytes: organ-selective localization in vivo and the role of lymphocyte-endothelial cell recognition.
Authors: Stevens S K , Weissman I L , Butcher E C 
Published: December 2022

Abstract
The migration of B and T lymphocytes in the mouse has been studied by using 1) short-term in vivo homing studies, and 2) an in vitro assay of lymphocyte binding to specialized lymphoid organ venules (post-capillary, high endothelial venules (HEV)) in frozen sections of lymph nodes and Peyer's patches. The homing characteristics of B and T cell populations are largely independent of their organ of origin. B cells from any source distribute preferentially to Peyer's patches, whereas T cells home preferentially to peripheral lymph nodes. This organ specificity of migration appears to be determined at the site of lymphocyte exit from the blood by selective recognition of organ-specific determinants on the endothelial cells of HEV. In addition, the in vivo tendency of B cells to migrate preferentially to the spleen, and of T cells to localize better in lymph nodes is confirmed. The results indicate that, in a hypothetical situation in which an equal number of B and T lymphocytes localized in peripheral lymph nodes (or bound in vitro to peripheral node HEV), there would be about 2.5 B cells for every T cell in the mesenteric node, four to six B cells per T cell in Peyer's patches, and seven to nine B cells per T cell in the spleen. Comparison of these homing preferences with the distribution of B and T lymphocyte populations in situ suggests that selective lymphocyte migration may help determine the proportions of functionally distinct lymphocyte classes in particular lymphoid organs or sites of chronic inflammation, and thus may serve to influence the character of local immune responses.
Mechanism of enhanced complement-dependent cytotoxicity of papain-treated lymphocytes: evidence for increased stability of classical pathway C3 convertase.
Authors: Lublin D M , Grumet F C 
Published: December 2022

Abstract
The mechanisms of enhanced antibody-mediated, complement-dependent cytotoxicity caused by proteolytic treatment of cells was studied in a model system based on HLA microlymphocytotoxicity methods. In this model, papain treatment of lymphocytes resulted in a) no change in antibody binding, b) a slight decrease in initial binding of C4, c) a marked increase in stability of cell-bound C4b, resulting in d) an increase of cell-bound C3, and e) no increase in lytic efficiency of the C5b-9 membrane attack complex. We conclude that the most important step in papain enhancement of lysis of lymphocytes is an increased stability of cell-bound C4b, possibly through decreased surface binding of C4-bp. This mechanism may be relevant to the pathologically increased lysis of cells occurring in patients with hereditary erythroblastic multinuclearity with a positive acidified-serum test (HEM-PAS).
Microinjection of macromolecules into normal murine lymphocytes by cell fusion technique. I. Quantitative microinjection of antibodies into normal splenic lymphocytes.
Authors: Ohara J , Watanabe T 
Published: December 2022

Abstract
Human erythrocyte ghosts loaded with various kinds of protein molecules were fused with mouse splenic lymphocytes by means of polyethylene glycol supplemented with poly-L-arginine and dimethylsulfoxide. This fusion method made quantitative microinjection of IgG and other proteins into intact lymphocytes possible. The injection itself did not alter cell viability, and lymphocytes given protein molecules retained intact response activity when they were stimulated with mitogens. Rabbit anticyclic AMP was purified by affinity chromatography and injected into lymphocytes. Antibody activity in the cell lysates was measured by using 125I-labeled cyclic AMP as an antigen, and it was shown that antibody molecules were quantitatively injected and immunologically active in the cells. Antigen binding activity of anti-cyclic AMP antibodies in the nonstimulated lymphocytes was stable and intact even 24 hr after microinjection, whereas the activity rapidly decreased in mitogen-stimulated lymphocytes, indicating that some immunologic or enzymatic mechanisms for inactivating antibodies were induced in mitogen-stimulated cells. Furthermore, microinjection of anti-cyclic AMP markedly enhanced the proliferative responses of lymphocytes to mitogens such as Con A or LPS and reversed the effect of a known elevator of intracellular cyclic AMP. These observations have implications for the role of cyclic AMP in early lymphocyte activation events.
The purification and properties of human T cell growth factor.
Authors: Mier J W , Gallo R C 
Published: December 2022

Abstract
Human T cell growth factor (TCGF) has been purified more than 800-fold from serum-free lymphocyte conditioned media by utilizing ion exchange chromatography with DEAE-Sepharose, gel filtration with Ultrogel AcA54, and preparative SDS-polyacrylamide gel electrophoresis. This mitogenic protein, which is released by T cells into the incubating media after exposure to a lectin (PHA), has a m.w. of 13,000 as determined by SDS-PAGE and 20,000 to 25,000 on gel filtration and has an isoelectric point of 6.8. The material extracted from acrylamide gels is a single band (or two nearly superimposed bands) when rerun on analytical SDS gels. Partially purified material is unstable even at -70 degrees C and requires the addition of bovine serum albumin or polyethylene glycol to maintain biologic activity. It is sensitive to proteolytic digestion but resistant to nucleases and thiol-reducing agents such as dithiothreitol. Human TCGF can be reversibly denatured with urea or SDS. Material extracted from acrylamide gels has been shown to sustain T lymphoblasts in tissue culture. In contrast to lectins, certain antigens, and crude lymphocyte conditioned media, purified TCGF does not initiate lymphocyte blastogenesis but is a highly selective mitogen for T cells previously activated by exposure to lectins or antigens.
Anti-RNP monoclonal antibodies derived from a mouse strain with lupus-like autoimmunity.
Authors: Billings P B , Allen R W , Jensen F C , Hoch S O 
Published: December 2022

Abstract
systemic lupus erythematosus (SLE) and related rheumatic and connective-tissue diseases are often associated with the production of antibodies directed against a variety of specific cellular components. Recent evidence indicates that two such autoantigens, the Sm and RNP antigens recognized by SLE sera, exist in small ribonucleoprotein complexes found in the nuclei of higher eukaryotes. Studies of the structure and function of these autoantigenic particles with human sera used as probes have been limited because of the multiplicity of autoantibodies often found in an individual serum. Through this communication, we report that MRL/Mp-+/+ (MRL/n) mice, which spontaneously develop a disease exhibiting many of the characteristics of human SLE, possess anti-RNP antibodies in addition to anti-Sm and anti-DNA as previously reported. Spleen cells from one such autoimmune mouse were used to produce a stable hybridoma secreting antibodies that react simultaneously with a protein of Mr 40,000 and a doublet of approximately 70,000, a pattern of reactivity identical to and characteristic of human SLE anti-RNP autoantibodies.
Sr++-induced inhibition of human natural killer (NK) cell-mediated cytotoxicity.
Authors: Neighbour P A , Huberman H S 
Published: December 2022

Abstract
The cell believed to be responsible for human spontaneous cytotoxicity or natural killing (NK) has been described recently as a large granular lymphocyte (LGL). Because the intracytoplasmic granules of LGL appear to be peculiar to the subpopulation of mononuclear cells containing NK effectors, we have investigated their possible requirement in the cytolytic process. Experiments reported here show that Sr++, a cation known to cause degranulation of granulocytes, caused a dose- and time-dependent inhibition of the NK activity of human peripheral blood mononuclear cells. A single-cell NK assay showed that the number of cytotoxic cells was not significantly reduced, but that Sr++ inhibited NK by preventing individual effector cells from engaging in multiple lethal hits. Moreover, the inhibition of NK appeared to be reversible; culture in vitro of Sr++-treated PBMC resulted in the eventual return of cytolytic activity in these cells. Augmentation of NK by interferon (IFN) was similarly blocked by Sr++. In addition, Sr++ also inhibited the NK activity of IFN-prestimulated effector cells and, as before, NK function returned during subsequent culture. These results indicated that the return of NK function after Sr++ treatment was the result of reactivation of cytotoxic cells rather than recruitment of new effectors. We have shown in other studies that Sr++ degranulates LGL, and the data presented here provide support for the hypothesis that the intracytoplasmic granules of LGL are required for NK-mediated cytotoxicity.
Monoclonal antibody to Mullerian inhibiting substance.
Authors: Mudgett-Hunter M , Budzik G P , Sullivan M , Donahoe P K 
Published: December 2022

Abstract
Mullerian Inhibiting Substance (MIS) is a testicular product that causes the regression of the Mullerian duct in the developing male embryo. Antibody specific for MIS would facilitate the purification and study of this "hormone," but because of its impure status, traditional polyclonal antisera specific for MIS would be untenable. The requisite specificity, however, might be obtained by the technique of somatic fusion, regardless of the purity of the immunizing antigen. This paper describes the production of 2 monoclonal antibodies specific for MIS by the technique of somatic cell fusion. Spleen cells from mice immunized with an impure preparation of MIS were fused with myeloma cell line NS1. Culture media from the resulting hybridoma cell lines were screened for anti-MIS antibody by a sensitive RIA. Specificity for MIS was demonstrated by the adsorption of biologically active MIS on an affinity column prepared from monoclonal anti-MIS antibody. MIS activity as assessed by an organ culture assay was subsequently recovered from the affinity column in the fraction eluted with MH4SCN. Using the RIA, monoclonal anti-MIS antibody was also shown to compete favorably with a variety of potentially cross-reactive proteins.
Anti-immunoglobulin stimulation of murine lymphocytes. VII. Identification of an age-dependent change in accessory cell function.
Authors: Scribner D J , Moorhead J W 
Published: December 2022

Abstract
Rabbit anti-mouse immunoglobulin-induced proliferation of murine B cells requires the participation of a macrophage- (M phi)like accessory cell. This cell is found in the spleen of aged mice, the B cells of which respond to stimulation by intact anti-Ig molecules. M phi characteristics of this cell include resistance to treatment with either anti-theta or anti-Ig plus complement, adherence to plastic, and resistance to radiation. Evidence was obtained that indicates that the age-dependent anti-Ig responsiveness of B cells involves, in part, a temporal change in the splenic M phi population. The ability of these accessory cells to facilitate anti-Ig responsiveness by normally unresponsive B cells was shown both in vivo and in vitro. Reconstitution of lethally irradiated aged, but not young, mice with spleen cells from unresponsive young mice resulted in the appearance of anti-Ig responsive B cells within 30 days. Similarly, coculture of unresponsive spleen cells with irradiated splenic adherent cells from aged, but not young, mice provided accessory cell activity for anti-Ig responses. Additional experiments showed that accessory cells were also present in bone marrow and the peritoneal cavity but were absent in lymph node and thymus. Addition of 2-mercaptoethanol to the culture medium functionally replaced the requirement for accessory cells and was also found to alter the response pattern of the B cells.
Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin A.
Authors: Wang B S , Heacock E H , Chang-Xue Z , Tilney N L , Strom T B , Mannick J A 
Published: December 2022

Abstract
Mice sensitized with alloantigens and treated with cyclosporin A (CsA) were incapable of generating antigen-specific cytolytic lymphocytes (CL). Lymphocytes from these CsA-treated animals could not be reactivated upon exposure to the same alloantigens in mixed lymphocyte culture (MLC), whereas their response to a third-party antigen remained intact, suggesting a long-lasting and specific effect of CsA. After being irradiated, these lymphocytes from CsA-treated animals were added to normal MLC and were shown to prevent normal lymphocytes from becoming cytolytic in a dose-dependent and antigen-nonspecific fashion. These suppressor cells were not detected in mice receiving CsA only, indicating that CsA did not induce but rather permitted the expression of suppressor cells possibly generated by allosensitization. The suppressor cells appeared to be T lymphocytes, because treatment with anti-Thy-1.2 antibody and C abrogated their suppressive activity. The present results suggest that activation and/or sparing of suppressor cells by CsA may account for the long-lasting unresponsiveness seen in CsA-treated animals.
Adoptive transfer of modulation of granuloma formation and hepatosplenic disease in murine schistosomiasis japonica by serum from chronically infected animals.
Authors: Olds G R , Olveda R , Tracy J W , Mahmoud A A 
Published: December 2022

Abstract
The course of disease due to Schistosoma japonicum in C57BL/6J mice was examined. Animals infected with 25 cercariae of the Philippine strain of S. japonicum for 9 wk develop a peak portal hypertension of 13 +/- 0.6 cm H2O and mean hepatic granuloma area of 459 X 10(3) micrometers 2. By 30 wk, disease manifestations were reduced; mean portal pressure was 7 +/- 0.5 cm H2O and mean hepatic granuloma area was 12 X 10(3) micrometers 2. Adoptive transfer of serum but not 1 X 10(8) spleen or 4 X 10(7) lymph node cells from chronically infected mice resulted in lowering portal pressure and decreasing granuloma size in recipients. Granuloma formation in the sensitized lung model was also suppressed by serum from chronically infected mice. The immunosuppressive component of this serum was localized in the IgG1 fraction.
Interactions of bacterial lipopolysaccharide with acute-phase rabbit serum and isolation of two forms of rabbit serum amyloid A.
Authors: Tobias P S , McAdam K P , Ulevitch R J 
Published: December 2022

Abstract
Mixing lipopolysaccharide (LPS, Salmonella minnesota R595) with acute-phase rabbit serum (APRS) results in the formation of two types of complexes. The two complexes are separable from each other and from LPS by CsCl density gradient ultracentrifugation. LPS alone had density 1.38 g/cm3, complex 1.3 had density 1.3 +/- 0.02 g/cm3, and complex 1.2 had density less than 1.20 g/cm3. At 1 to 10 micrograms LPS/ml APRS, up to 23 micrograms of LPS could be found in complex 1.3, with the remainder of the LPS in complex 1.2. The capacity of complex 1.2 for LPS was 500 to 600 micrograms LPS/ml APRS. The ability of rabbit serum to form complex 1.3 rose to a maximum in 24 hr post-acute-phase induction. The two complexes were purified by equilibrium density gradient ultracentrifugation and immunoaffinity chromatography using antibodies to LPS and subjected to SDS-PAGE. Complex 1.3 had major peptides after reduction of 91, 64, 61 and 50 kilodaltons. The 61-kilodalton peptide is probably rabbit serum albumin; the others are unidentified. Complex 1.2 had major peptides after reduction whose mobility corresponded to apolipoprotein A-I and serum amyloid A. Complex 1.2 thus seems to be analogous to the LPS-high-density-lipoprotein complexes that form in normal serum except that the latter complexes do not contain serum amyloid A. Rabbit serum amyloid A (SAA) was purified by CsCl equilibrium density gradient ultracentrifugation, gel filtration, and ion-exchange chromatography into two forms, SAA-1 and SAA-2. The two forms of SAA have very similar amino acid compositions and m.w. (SAA-1, 11,526 daltons; SAA-2, 11,469 daltons). They differ primarily in their isoelectric points, 6.57 and 6.27 for SAA-1 and SAA-2, respectively. The complexes 1.2 from several individual rabbits after acute-phase induction were studied by isoelectric focusing. Seven of 10 rabbits showed both forms of SAA; three showed a single form. Two rabbits showing SAA-1 on the first acute-phase induction were reinduced; one rabbit again gave SAA-1 and the other gave SAA-2. These results suggest that SAA and perhaps other acute-phase reactants may modulate the biologic activity of LPS.
Immunogenetics of BCG-induced anergy in mice: control by genes linked to the Igh complex.
Authors: Schrier D J , Sternick J L , Allen E M , Moore V L 
Published: December 2022

Abstract
The genetics of BCG-induced anergy was studied in mice by evaluating delayed hypersensitivity to sheep erythrocytes. Data obtained using congenic mice and by linkage analysis suggested that genes linked to the H-2 complex do not influence the development of anergy. However, studies in allotype-congenic partners (BALB/c; BALB.Igb) indicated that anergy was influenced by genes linked to the immunoglobulin heavy chain complex (Igh). Breeding studies indicated that the gene influencing anergy is recessive. These studies were extended by using BXD recombinant inbred mice, and verified that anergy is controlled by genes linked to the Igh complex. Because several markers and a tentative map has been constructed for the Igh complex on chromosome 12 in BXD mice, we suggest that the gene that controls BCG-induced anergy is located on the centrometric side of Igh-C approximately 18 to 28 recombination units.
Repertoires of T cells directed against a large protein antigen, beta-galactosidase. I. Helper cells have a more restricted specificity repertoire than proliferative cells.
Authors: Krzych U , Fowler A V , Miller A , Sercarz E E 
Published: December 2022

Abstract
The proliferative and helper T cell repertoires were compared in the CBA/J mouse for the response to the large protein antigen, tetrameric beta-galactosidase (GZ = 1021 a.a/monomer). The systems assessed the ability of cyanogen bromide (CB) peptides of GZ to: 1) prime for a T cell proliferative response to GZ; or 2) generate T cell help, measured by the production of anti-FITC PFC in the in vitro response to GZ-FITC. Priming for in vitro proliferation was attempted with 11 CB peptides comprising 70% of the GZ molecule. Strong priming was found with five peptides and intermediate priming was found with four other peptides; two peptides were without effect (CB-20 = a.a 767-862, and CB-4 = a.a. 188-202). Despite this indication of generally dispersed recognition of GZ epitopes, only two CB peptides, CB-2 (a.a. 3-92) and CB-10 (a.a. 378-418) were able to induce a T helper cell response. The surprising dearth of helper T cell-inducing epitopes may be peculiar to the limited fluorescein (FITC) substitution on GZ-FITC (17-25 FITC residues per tetramer) or it may reflect the constraints involved in T cell recognition required for T-B collaboration. Also considered was the possibility that the helper T cell repertoire might be distinct from the proliferative repertoire, the latter reflecting DNA synthesis and recruitment by other functional T cell subpopulations.
Antigenic requirement for induced rejection of long-surviving murine heart transplants.
Authors: Burdick J F , Russell P S 
Published: December 2022

Abstract
Primarily vascularized B10.BR mouse cardiac allografts survive long-term in untreated B6AF1 recipients. We found that sudden complete rejection of the grafts was produced by sequential "triple treatment" with BCG, cyclophosphamide, and a small number of donor-strain lymphocytes. Neither the graft itself, nor donor-strain platelets or frozen-thawed lymphocytes were an effective substitute for the intact donor-strain lymphocytes. Thus the long-surviving graft presents target antigens but lacks the antigenic characteristics required to stimulate a rejection response that are expressed on lymphocytes.
Helper cell factors restore antibody responses of allogeneic bone marrow chimeras: evidence for ineffective cellular interactions.
Authors: Coico R F , Krown S E , Good R A , Hoffmann M K 
Published: December 2022

Abstract
We investigated the nature of deficient antibody responses to SRBC in stable, fully allogeneic bone marrow chimeras. No evidence for a suppressor cell-mediated mechanism was found. Chimera spleens possessed adequate numbers of antigen-reactive B cells to produce a normal antibody response. Using separated chimera cell populations and soluble helper factors, we assessed the functional capabilities of chimera B cells, T cells, and macrophages. Our data suggest that the failure of allogeneic chimeras to produce antibody is not the result of impaired B cell, T cell, or macrophage function, but rather that it is due in ineffective cellular interactions that normally result in the generation of helper factors. In vitro stimulation of chimera macrophages with LPS, and of chimera spleen cells with Con A, resulted in the release of soluble helper factors that were capable of fully restoring chimera B cell responses.
Monoclonal antibody against human interleukin 2 (IL 2). I. Purification of IL 2 for the production of monoclonal antibodies.
Authors: Stadler B M , Berenstein E H , Siraganian R P , Oppenheim J J 
Published: December 2022

Abstract
Human interleukin 2 (IL 2) was produced under serum-free conditions by stimulating mononuclear cells with concanavalin A (Con A) in the presence of phorbol myristate acetate (PMA) and hydroxyurea. The IL 2 was partially purified by sequential chromatography by using phenyl-Sepharose, DEAE Sephacel, and AcA 54 gel filtration. This partially purified material was used to immunize BALB/c mice. After immunization with a total of 48,000 U (spec. act. approximately 10(5) units/mg protein), the spleen cells were adoptively transferred into x-irradiated syngeneic mice and the animals were boosted with another 12,000 U of IL 2. Four days later their spleen cells were hybridized with plasmacytoma cells. Supernatants of the hybridoma cultures were screened for their capacity to inhibit the IL 2-induced proliferation of the CT6 cell line. After expansion and cloning eight different lines were selected for ascitic antibody production. The monoclonal antibodies inhibited the proliferation of the IL 2-dependent cell line in response to either human crude or purified IL 2, as well as rat and mouse IL 2. However, these anti-IL 2 antibodies did not inhibit the proliferation of human T cell lines capable of producing IL 2. Monoclonal antibodies coupled to Sepharose 4B absorbed IL 2 crude culture supernatant, confirming that they react directly with IL 2. The absorbed IL 2 could, for the most part, be eluted by using sodium dodecyl sulfate, thus providing a means for further immunoaffinity purification of IL 2.
Characterization of the human cellular immune response to purified group A streptococcal blastogen A1.
Authors: Regelmann W E , Gray E D , Wannamaker L W 
Published: December 2022

Abstract
The human mononuclear cell response to purified extracellular streptococcal protein, blastogen A, was compared to the response of these cells to PHA and tetanus antigen. Blastogen A induced peak uptake of thymidine during day 6 of tissue culture whereas PHA induced peak uptake during day 5 and tetanus during day 8. Like PHA, blastogen A transformed human umbilical cord lymphocytes and those of nonimmune animals. Also like PHA, blastogen A transformed primarily T lymphocytes. However, unlike PHA, the ability of T lymphocytes to respond to blastogen A was almost completely dependent on the presence of viable non-T lymphocytes. Monocytes were not as effective in facilitating the response to blastogen A as they were for PHA. Thus, blastogen A behaves most like a polyclonal T lymphocyte mitogen, although the degree of dependence of the transformation response on the presence of non-T lymphocytes is much greater than that of PHA.