bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo.
Authors: Kohl S , Loo L S , Schmalstieg F S , Anderson D C 
Published: December 2022

Abstract
The role of the Mac-1, LFA-1, p150,95 leukocyte glycoprotein family in mediating antiviral host defense was investigated by utilizing mononuclear cells (MC) obtained from eight patients with a genetic deficiency of Mac-1, LFA-1, and p150,95, and normal MC incubated with subunit-specific monoclonal antibodies (MAb) directed against these glycoproteins. As shown with an in vitro chromium-release cytotoxicity assay to herpes simplex virus (HSV)-infected Chang liver target cells, MC of these patients with the severe phenotype or normal MC preincubated with a combination of MAb against Mac-1 glycoprotein subunits were deficient in antibody-dependent cellular cytotoxicity (ADCC). When used individually, MAb directed at LFA-1-alpha or -beta also inhibited ADCC and natural killer cytotoxicity (NKC). In a single cell agarose assay, MC of Mac-1-deficient patients formed fewer effector-target cell conjugates in the presence of specific anti-HSV antibody. To investigate the in vitro contributions of these glycoproteins to cytotoxic host defense mechanisms, two in vivo adoptive transfer models were explored in which neonatal mice are protected against a lethal HSV challenge by normal human MC plus anti-HSV antibody (in vivo ADCC) or human interferon-alpha (NKC stimulated in vivo). In each model, MC from patients with "severe" or "moderate" phenotypes of Mac-1 deficiency, or normal MC incubated with a combination of anti-LFA-alpha, Mac-1-alpha, p150,95-alpha plus -beta MAb failed to protect neonatal mice against lethal HSV infection. These studies further indicate requirements for adhesion-dependent mechanisms in the mediation of MC-ADCC, and suggest that Mac-1-dependent cellular adhesive properties are necessary for normal cytotoxic functions in vivo in experimental models of human ADCC or interferon-stimulated NKC. These findings, in addition to the recognized occurrence of severe or even lethal viral infections in some Mac-1-deficient patients, suggest that glycoproteins of the Mac-1 family may be important determinants of antiviral host defense.
Involvement of natural killer cells in coxsackievirus B3-induced murine myocarditis.
Authors: Godeny E K , Gauntt C J 
Published: December 2022

Abstract
The role of natural killer cells in the temporal development of coxsackievirus B3-induced myocarditis in adolescent CD-1 male mice was examined. Inoculation of purified CVB3m induced maximum NK cell activity in the splenic populations at 3 days postinoculation (p.i.) as assessed by lysis of YAC-1 cells; maximum virus titers in heart tissues were also found at day 3 p.i. Mice depleted of NK cells after injection of anti-asialo GM1 antiserum i.v. had decreased NK cell activity, increased CVB3m titers in heart tissues, and exacerbated myocarditis. Although lesion number was not increased in heart tissues of the latter mice, lesions in these mice exhibited increased myocyte degeneration and dystrophic calcification above that found in lesions of mice inoculated with CVB3m only. No alteration in interferon titers were observed in CVB3m-infected mice treated with anti-asialo GM1 antiserum as compared with normal CVB3m-infected mice. Measurements of splenic NK cell activity in mice inoculated with doses of 10(2) to 10(8) PFU of CVB3m per mouse or UV-irradiated virus suggest that replication of CVB3m is required for NK cell activation. An amyocarditic variant of CVB3m (ts5R) was shown to replicate in heart tissues and to elicit NK cell activity comparable to that elicited by CVB3m. Therefore, the data suggest that NK cell activation depends on virus replication and that these cells provide some protection against CVB3m-induced myocarditis by limiting virus replication in heart tissues.
Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide-tetanus toxoid conjugate vaccine.
Authors: Jennings H J , Roy R , Gamian A 
Published: December 2022

Abstract
Conjugation of the group B meningococcal polysaccharide to tetanus toxoid failed to substantially enhance its immunogenicity in mice. Therefore, additional chemical manipulation of the basic structure of the group B meningococcal polysaccharide was attempted, on the premise that a synthetically derived artificial antigen might be capable of modulating the immune response in mice to produce elevated levels of cross-reactive group B meningococcal polysaccharide-specific antibodies. To achieve this, the antigenicity of the modified polysaccharide to group B meningococcal polysaccharide-specific antibodies had to be preserved, and this criterion could only be satisfied in modifications in which the carboxylate and N-carbonyl groups of the sialic acid residues of polysaccharide remained intact. Therefore, the most successful modifications were accomplished by N-deacetylation of the group B meningococcal polysaccharide with strong base to yield a precursor that could then be N-acetylated or N-arylated with different substituents. For example, the introduction of N-propionyl groups, followed by conjugation of the resultant N-propionylated group B meningococcal polysaccharide to tetanus toxoid, yielded an antigen that when injected in mice induced in them high levels of cross-reactive group B meningococcal polysaccharide-specific IgG antibodies. The T cell dependency of this antigen was established when it was demonstrated that the levels of these B polysaccharide-specific antibodies could be significantly boosted by using both the N-propionylated- and native N-acetylated-group B meningococcal polysaccharide-tetanus toxoid conjugates.
A variable region gene subfamily encoding T cell receptor beta-chains is selectively conserved among mammals.
Authors: Marche P N , Kindt T J 
Published: December 2022

Abstract
Studies of murine T cell receptor genes indicate that the VT beta repertoire, in contrast to the large VT alpha, VH, and VK repertoires, is limited to approximately 21 genes. Large differences between the various VT beta sequences allow classification into distinct subfamilies consisting of one or few members. The VT beta sequence of a gene, RTB92, expressed in a rabbit T cell line is most closely related to a VT beta gene expressed in the human cell line Molt-4. Genomic blots with RTB92 VT beta region used as probe indicated conservation of related VT beta gene subfamilies in man and pig, but no related sequences were seen in rat, mouse, or hamster. The relationship among these VT beta genes mirrors similarities and differences in MHC genes of the compared species and suggests coordinate evolution of these functionally related gene families. The constant region of RTB92 was shown to be rabbit CT beta 2 by reference to genomic clones. Comparisons with constant region sequences of human and murine CT beta 1 and CT beta 2 chains reveal no similarities in amino acid or nucleic acid sequence in the coding region characteristic of the respective isotypes. Intraspecies homologies between CT beta 1 and CT beta 2 sequences were much greater than those between CT beta 1 or CT beta 2 from other species. By contrast, comparisons of JT beta and 3' untranslated region sequences showed significant interspecies conservation of sequences in the beta 1 and in the beta 2 regions.
Tumor-specific idiotype vaccines. I. Generation and characterization of internal image tumor antigen.
Authors: Raychaudhuri S , Saeki Y , Fuji H , Kohler H 
Published: December 2022

Abstract
The concept of idiotype vaccines against tumor-associated antigens (TAA) was tested in the DBA/2 L1210 lymphoma subline, L1210/GZL. Monoclonal antibodies against a TAA that cross-reacts with the envelope glycoprotein gp52 of the mammary tumor virus were used to make hybridoma anti-idiotype antibodies (Ab2). In this report we describe the characterization of monoclonal anti-idiotypic antibodies against the combining site of 11C1 (Ab1), which recognizes a shared determinant of gp52 of mouse mammary tumor virus (MMTV) and the TAA of L1210/GZL. Hybridomas expressing the internal image of gp52 were screened by an idiotype inhibition assay. Mice sensitized with radiated L1210/GZL cells produced specific delayed type hypersensitivity (DTH) against the Ab2 hybridoma. Five Ab2 hybridomas were selected and were used to immunize DBA/2 mice. Such immunized animals showed specific DTH reaction against a challenge with the L1210/GZL tumor cells. Similar results were obtained in mice immunized with purified Ab2. Fluorescence-activated cell sorter analysis demonstrated that fluorescence staining of L1210/GZL cells by 11C1 can be completely inhibited with preabsorption on Ab2 hybridoma cells. Mice immunized with 2F10 and 3A4 coupled to keyhole limpet hemocyanin (KLH) contained antibodies binding to MMTV. But only in mice immunized with 2F10-KLH was significant inhibition of L1210/GZL tumor growth observed. Collectively, these results indicate that certain anti-idiotypic antibodies can mimic the MMTV gp52 antigen, as well as the gp52-like epitope expressed on the L1210/GZL tumor cells. These properties of anti-idiotypic antibodies mimicking TAA could be exploited for making idiotype vaccines against tumors.
Role of DNA synthesis in secretion of immunoglobulin from murine B cells stimulated by T cell derived lymphokines.
Authors: Simpson L G , Isakson P C 
Published: December 2022

Abstract
We have investigated whether cell division is required for induction of Ig secretion from three types of B cells, which represent distinct activation states: normal splenic B cells, anti-Ig-treated B cells, and a monoclonal murine B cell tumor, BCL1. Polyclonal Ig secretion was stimulated in vitro by LPS or by lymphokines produced by EL-4 cells (EL-4 SN), which includes B cell growth factor II (BCGF II). LPS and EL-4 SN were mitogenic for all three cell populations and stimulated substantial IgM secretion from both B cells and anti-Ig blasts. Aphidicolin, a reversible inhibitor of DNA synthesis, abolished IgM secretion from B cells and anti-Ig blasts induced by either mitogen, indicating that Ig-secreting cells in these cultures are part of a cycling population. BCL1 tumor cells respond to BCGF II (but not to interleukin 2 or B cell stimulatory factor 1) with IgM secretion and cell division, allowing a direct assessment of the influence of BCGF II-stimulated cell division on secretion of IgM. Secretion by these cells during the first 24 hr of culture was not substantially affected by aphidicolin, but secretion at 48 or 72 hr was markedly inhibited. Culture of BCL1 cells for 48 hr with aphidicolin alone had no effect on cell viability or on subsequent responsiveness if the drug was removed, eliminating non-specific toxicity as an explanation of the drug's effect. Addition of aphidicolin during the last 24 hr of culture to either normal B cells or BCL1 cells was much less effective at inhibiting IgM secretion. These results indicate that the cells that secrete IgM in response to BCGF II also synthesize DNA when exposed to this factor. Thus, induction of high-rate Ig secretion from murine B cells by some stimuli, including BCGF II, may require at least one round of cell division.
Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3.
Authors: Ceuppens J L , Baroja M L 
Published: December 2022

Abstract
Activation of human peripheral blood T cells by the anti-CD3 antibody OKT3 has been shown to require not only cross-linking of CD3 molecules with multimeric binding of the Fc part of OKT3 to a solid support, but also a second accessory cell-provided signal. Accordingly, measurement of T cell activation in cultures of highly enriched T cells with solid-phase-bound OKT3 can be used to investigate whether other agents can replace accessory cells. In this study we examined the capacity of anti-CD5 monoclonal antibodies to provide the additional activation signal. Resting T cells were prepared by isolating E rosette-positive cells, by removing OKM1(+) and HLA-DR(+) cells by panning, and by subsequent treatment of the cells with L-leucine methyl ester to kill remaining monocytes. These T cells were unresponsive to phytohemagglutinin (PHA) or to solid-phase-bound OKT3. However, when cultured in the presence of an anti-CD5 monoclonal antibody (anti-Leu-1, OKT1, or anti-T1), a proliferative response to solid-phase-bound OKT3 (but not to soluble OKT3 or to PHA) was observed. Anti-CD5 had no functional effect by itself, but in association with solid-phase-bound OKT3 it enhanced IL 2 receptor expression and IL 2 production and it initiated T cell proliferation. T cell proliferation under these conditions could be inhibited by an IL 2 receptor blocking antibody anti-Tac, thus confirming that anti-CD5 provides the second signal for an IL 2-dependent pathway of T cell proliferation. Preincubation of T cells with anti-Leu-1 or OKT1 resulted in complete loss of CD5 antigenicity, and such CD5 modulation was sufficient to induce a proliferative response to solid-phase-bound OKT3. It is concluded that in T cell activation by solid-phase-bound OKT3 the necessary additional signal can be provided by modulation of the CD5 antigen with an anti-CD5 antibody. CD5 therefore appears to be a positive signal receptor on the T cell membrane, whose physiologic ligand still has to be determined.
The regulatory role of NZB T lymphocytes in the production of anti-DNA antibodies in vitro.
Authors: Laskin C A , Haddad G , Soloninka C A 
Published: December 2022

Abstract
Murine lupus is characterized by the production of numerous autoantibodies and immune complex glomerulonephritis. Anti-DNA antibodies are the hallmark of this disorder and may be associated pathogenetically with the glomerulonephritis. The cellular mechanisms underlying the regulation of the production of anti-DNA antibodies may prove to be the fundamental abnormalities responsible for the lupus syndrome seen in these mice. By using a system of spontaneous anti-DNA antibody production in vitro, we have determined that such production is characteristic of autoimmune NZB and MRL-lpr/lpr mice but not of the nonautoimmune control strains. Additional examination of the cellular mechanisms involved in the regulation of this response in NZB mice revealed: 1) this response is markedly T cell dependent, 2) NZB T cells are essential for maximal production of this autoantibody, and 3) NZB T cells actively interfere with normal immune regulatory mechanisms that lead to the production of anti-DNA antibodies spontaneously in vitro by nonautoimmune syngeneic B lymphocytes. Although these studies of anti-DNA antibody production in vitro disagree with previous work by others they successfully reproduce the results obtained earlier in experiments performed in vivo.
The human LT system. XI. Identification of LT and "TNF-like" forms from stimulated natural killers, specific and nonspecific cytotoxic human T cells in vitro.
Authors: Yamamoto R S , Ware C F , Granger G A 
Published: December 2022

Abstract
These studies demonstrate that specific and nonspecific cytolytic human T cells can release LT forms in vitro. Nonspecific cytolytic T cells were derived from IL 2-dependent cultures initiated by allogeneic mixed lymphocyte reaction (AMLR). Specific cytolytic T cells (CTL) were derived from IL 2-dependent T cell clones, initiated by mixed lymphocyte reaction and specific for class II antigens. alpha-LT was the major lytic component released by these cells in IL 2-dependent cultures. However, on Con A stimulation or contact with target cells, both AMLR and CTL effectors release a new LT form. The new LT form released by AMLR and CTL effectors appear similar, for they both elute from gel filtration at 60,000 to 70,000 m.w. and migrate as a single peak with an Rf of 0.4 on 7% native PAGE tube gels. Moreover, testing these materials on a panel of target cells in vitro indicates that they are both nonspecific, and lyses NK-resistant target cells in vitro. Additional studies revealed that in vitro lytic activity of this form(s) is not affected by either anti-alpha-LT serum or a monoclonal reagent which inactivates macrophage cell toxins (MCT) and tumor necrosis factor (TNF). However, when these two immunologic reagents are tested together, activity is totally neutralized. Thus, this LT form expresses antigens in common with alpha-LT, MCT, and TNF. Finally, studies with NK-CF and NK-LT forms revealed that they were also completely neutralized with a mixture of anti-LT and monoclonal anti-TNF antibody. These data suggest that certain macrophage- and lymphocyte-derived cell toxins are interrelated.
Structural analyses of a monoclonal heterodimeric suppressor factor specific for L-glutamic acid60-L-alanine30-L-tyrosine10.
Authors: Turck C W , Kapp J A , Webb D R 
Published: December 2022

Abstract
A GAT-specific, MHC-restricted "second-order" suppressor T cell factor (TsF2) from the hybridoma 762 B3.7 was biosynthetically radiolabeled with 35S-methionine and was isolated from cell extracts. The isolation procedure involved two-dimensional nonreducing/reducing SDS-PAGE and electroelution of the reduced off-diagonal polypeptide chains from the gel. Biochemical characterization studies revealed that TsF2 is a disulfide-linked heterodimer composed of a basic and an acidic polypeptide chain, both having m.w. of 30,000. Both chains are glycosylated and contain sialic acid residues. The basic polypeptide reacts with anti-I-J antisera, whereas the acidic chain contains the antigen-binding capacity. Monoclonal antibodies induced by immunizing rats with TsF2 purified from hybridoma supernatants were selected for the ability to block immunosuppression mediated by TsF2 in vitro. These antibodies, but not irrelevant antibodies, immunoprecipitated the 35S-methionine-labeled protein that migrates off the diagonal in two-dimensional gels. Thus, we have verified that the immunosuppressive protein that migrates off the diagonal in two-dimensional gels binds to antibodies that are known to inhibit the biologic activity of unpurified TsF2.
Lymphocyte suppressive peptides from fibrinogen are derived predominantly from the A alpha chain.
Authors: Plow E F , Edgington T S 
Published: December 2022

Abstract
Cellular immune responses can elicit local deposition of fibrin at the site of immunologic reactions, as well as the formation of intravascular fibrin in disseminated reactions. The subsequent physiologic proteolysis of fibrinogen and fibrin by plasmin results in small peptides that suppress lymphocyte functions in vitro and in the immune response in vivo. The intramolecular origin of lymphocyte suppressive activity and the proteolytic events responsible for the release of active peptides have been analyzed. Plasmic peptides from the isolated B beta and gamma constituent chains of fibrinogen did not inhibit mitogen-driven responses of human peripheral blood mononuclear cells. In contrast, plasmic digests of the A alpha chain, but not the intact A alpha chain were suppressive. Advanced plasmic digests of fibrinogen and the A alpha chain were suppressive at similar concentrations, suggesting that biological activity is derived predominantly from the A alpha chain. Limited plasmic digests of fibrinogen were fractionated to yield a heat-precipitable 250,000 dalton fragment X and heat-soluble proteolytic products containing fragments derived from the carboxyl-terminal region of the A alpha chain including a 42,000 dalton major A alpha chain derivative. Neither fragment X nor derivatives produced by its additional plasmic proteolysis were suppressive. In contrast, the heat-soluble fraction from limited plasmic cleavage was suppressive, and this activity was enhanced 10-fold by additional plasmic cleavage of this fraction. The isolated 42,000 dalton A alpha chain fragment was devoid of activity, but plasmic digestion of this derivative generated peptides of less than 8000 daltons that inhibited mitogen-stimulated thymidine uptake by lymphocytes. Two synthetic peptides corresponding to A alpha 220-230 and B beta 43-47, peptides with known vasoactive activities, suppressed lymphocyte thymidine uptake at very high concentrations. Based on their maximal yield from plasmic digests of fibrinogen, these two peptides would account for only 1% of the immunosuppressive activity of fibrinogen derivatives. In summary, the results indicate that the suppressive activity of fibrinogen is predominantly derived from the 42,000 dalton carboxyl terminal region of the A alpha chain of the molecule and is not attributable to the known vasoactive peptides. Initial proteolytic release of this region from the core of fibrinogen does not result in suppressive activity, but additional cleavage releases small peptides with the lymphocyte inhibitory function.
Calcium modulation and chemotactic response: divergent stimulation of neutrophil chemotaxis and cytosolic calcium response by the chemotactic peptide receptor.
Authors: Meshulam T , Proto P , Diamond R D , Melnick D A 
Published: December 2022

Abstract
Stimulation of neutrophils by chemoattractants is followed by a rapid, transient rise in cytosolic calcium concentration. The role of calcium in activation of cell movement and related responses was examined by selectively chelating extracellular or both extra- and intracellular calcium. Removal of calcium from the extracellular medium did not alter the cytosolic calcium concentration (Quin 2 fluorescence, 110 to 120 nM) of unstimulated neutrophils and did not dramatically affect the rise induced by formyl peptide. Despite the intact Quin 2 response, depletion of extracellular calcium partially inhibited chemotaxis, adherence to substrate, and polarization (increased forward light scatter) in response to formyl peptide. Loading neutrophils with Quin 2 in the absence of calcium depressed cytosolic Ca2+ to 10 to 20 nM and abrogated a detectable rise with formyl peptide stimulation. Depletion of intracellular calcium further inhibited chemotaxis and polarization, although neutrophils still demonstrated significant directed migration and shape change to formyl peptide (30 to 40% of control) without an increase in Quin 2 fluorescence. Other neutrophil responses related to chemotaxis (decreased right-angle light scatter, actin polymerization) were minimally affected by depletion of calcium from either site. The data indicate that neutrophil chemotaxis and related responses to formyl peptide may be activated by intracellular signals not detectable with Quin 2.