bluuebunny/crossref_metadata_2025 huggingface dataset:
Cells mediating graft rejection in the mouse. I. Lyt-1 cells mediate skin graft rejection.
Authors: Loveland B E , Hogarth P M , Ceredig R , McKenzie I F
Published: June 2004

The Ly phenotype of cells mediating skin graft rejection was determined using monoclonal anti-Lyt-1.1 and Lyt-2.1 antibodies in CBA mice that received CBA lymphoid cells from mice sensitized to C57BL/6; i.e., alloantigenic differences arising from the H-2 and non-H-2 loci. It was clear that graft rejection was due wholly to the presence of Lyt-1 cells in the inoculum and that Lyt-123 or Lyt-23 cells had no effect. Furthermore, no synergism was noted between Lyt-1 and Lyt-2 cells. In this model, both the cytotoxic T cell and cytotoxic lymphocyte precursors were shown to be Lyt-123 and these could be depleted from sensitized Lyt-1 populations that mediated graft rejection. Thus cytotoxic T cells are not responsible for skin graft rejection, but rather, this is mediated by an Lyt-1 cell. Whether this T cell is distinct from other Lyt-1 cells (T helper, T cells mediating delayed hypersensitivity) is not clear at present, but other evidence, and traditional concepts, link graft rejection and delayed type hypersensitivity as being different manifestations of the same mechanism.
A monoclonal antibody that detects a V kappa-TEPC15 idiotypic determinant cross-reactive with a Thy-1 determinant.
Authors: Pillemer E , Weissman I L
Published: June 2004

To identify T lymphocyte antigens with immunoglobulin-like determinants, we prepared rat anti-mouse T cell monoclonal antibodies and screened them against a panel of purified mouse myeloma proteins representing all isotypes of immunoglobulin. One hybridoma, designated 42-21, was found to detect a novel antigenic determinant shared by V kappa-TEPC15 and the Thy-1 molecule on all T lymphocytes. Although several explanations for this unusual phenomenon exist, it may imply some role for the Thy-1 molecule in antigen and/or mitogen recognition. In any event, future studies of idiotypes on T lymphocytes must consider the possibility that anti-idiotypic sera detect cell surface molecules unrelated to classical immunoglobulin.
Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene.
Authors: Soloski M J , Uhr J W , Flaherty L , Vitetta E S
Published: June 2004

The Tla region located on the murine 17th chromosome controls several serologically defined cell surface antigens. These antigens, referred to as Qa-1-5 and TL, are expressed on a variety of hematopoeitic cell populations. In the present studies we have immunoprecipitated isotopically labeled Qa-2 and H-2 molecules from mitogen-stimulated B6 spleen cells. Sequential immunoprecipitation experiments have shown that the determinants recognized by alpha Qa-2, alpha H-2Kb, and alpha H-2Db alloantisera reside on separate molecular species. Comparative mapping of the arginine-labeled tryptic peptides from Qa-2, H-2Kb, and H-2Db molecules indicate that Qa-2 is structurally distinct but that there is considerable structural homology; 21-43% of the Qa-2 peptides co-chromatograph with peptides derived from H-2Db and H-2Kb, respectively. Similar levels of homology are observed when Qa-2 is compared with H-2Kk or H-2Dd. The results show that the Qa-2 alloantigen is encoded by a locus separate from the loci encoding H-2K or H-2D alloantigens, but that the Qa-2, H-2K, and H-2D alloantigens are sufficiently related at the primary structural level to indicate that they evolved from a common primordial gene.
The xid gene controls Ia.W39-associated immune response gene function.
Authors: Rosenwasser L J , Huber B T
Published: June 2004

Immune response (Ir) genes are encoded for by the I region of the major histocompatibility complex (MHC). A class of serologically defined specificities, Ia antigens, is also encoded for by genes within this region. A new Ia specificity, Ia.W39, has recently been defined. It is private for I-Ab and its expression is controlled by a gene on the X-chromosome. Using different approaches, the role of Ia.W39 in the immune response of H-2b mice to beef insulin was examined in a macrophage-dependent T cell proliferation assay. It was found that beef insulin-related Ir gene function was associated with the expression of Ia.W39 by antigen-presenting macrophages and that control of this Ir gene function was X-linked (xid gene).
Complement receptor is an inhibitor of the complement cascade.
Authors: Iida K , Nussenzweig V
Published: June 2004

A glycoprotein from the membrane of human erythrocytes has been identified as a receptor for C3b (CR1). It promotes the dissociation of the alternative pathway C3 convertase C3b,Bb and the cleavage of C3b by C3b/C4b inactivator. We find that CR1 also inactivates the C3 and C5 convertases of the classical pathway. CR1 inhibits the consumption of C3 by C3 convertase EAC142 and enhances the decay of C4b,2a sites. On a weight basis, CR1 is approximately 5-10 times more active than C4 binding protein, a serum inhibitor of C4b,2a. The binding of 125I-CR1 to EAC14 cells is inhibited by C2. Therefore, it is likely that CR1 and C2 compete for a site on C4b. CR1 inhibited C5 convertase even more effectively, but had no effect on the assembly of the late complement components. At high concentrations, CR1 alone has no irreversible effects on cell-bound C4b. In the fluid phase, CR1 can function as a cofactor for the cleavage of the alpha' chain of C4b by C3b/C4b inactivator. A well-known function of CR1 is to promote adherence of microbes or immune complexes bearing C3b and C4b to cells. This interaction could result in a microenvironment damaging to the plasma membrane of the responding cell because the extrinsic C3b and C4b fragments can serve as additional sites of assembly of enzymes of the cascade. We therefore wish to propose that CR1 on the surface of cells supplies an increased local concentration of a strong inhibitor of the amplifying enzymes of the complement system and provides cells with a mechanism for circumventing damage when they bind C3b- and C4b-bearing substrates.
Identification of retroviral gp70 and anti-gp70 antibodies involved in circulating immune complexes in NZB X NZW mice.
Authors: Izui S , Elder J H , McConahey P J , Dixon F J
Published: June 2004

Retroviral gp70 and anti-gp70 antibodies were isolated from circulating immune complexes (IC) of 7-10-mo-old (NZB X NZW)F1 mice, after which the nature and origin of this gp70 (IC-gp70) and the immunologic characteristics of these anti-gp70 antibodies (IC-anti-gp70) were investigated. Immunochemical and structural analyses of IC-gp70 demonstrated that among multiple immunologically related gp70 expressed in all mice, the IC-gp70 had characteristics similar to those of NZB xenotropic viral gp70 (NZB-X1 gp70) that is commonly present in sera of virtually all strains of mice. The study of binding by IC-anti-gp70 antibodies to retroviral gp70 from various sources showed that the IC-anti-gp70 were primarily directed to NZB-X1 gp70 as well as serum gp70. These data strongly suggest that the abnormality of murine strains with systemic lupus erythematosus causing them to produce antibodies to their own xenotropic viral gp70 and to form IC with serum gp70 is not based on their expression of an unusual type of gp70, but rather their ability to make an antibody to NZB-X1 gp70, probably as a result of their immunologic dysfunction.
Demonstration of a human pyrogen-inducing factor during mixed leukocyte reactions.
Authors: Dinarello C A
Published: June 2004

The role of lymphocytes in the pathogenesis of fever was investigated by stimulating human blood mononuclear cells in a two-way mixed leukocyte reaction (MLR). After 2-7 d of incubation, MLR supernates contained a factor that was not pyrogenic itself when injected into rabbits; however, these supernates, when incubated with human blood monocytes from a third donor, induced the synthesis of LP. The pyrogen-inducing activity was stable at 56 degrees C, destroyed at 70 degrees C, and was neither dialyzable nor removable by adsorption by anti-human leukocytic pyrogen (LP) attached to Sepharose 4B. Production of this factor was not always correlated with increased thymidine incorporation in the MLR. Its production was absent when peripheral lymphocytes were purified over nylon wool. The concentration of mononuclear cells in the MLR varied from 5 X 10(5) to 5 X 10(6)/ml in round-bottomed tubes. Under the latter conditions, some donor cells produced this factor without stimulation in the MLR culture, but when these cells were cultured on flat-bottomed containers at low cell concentration, autologous production was not observed. These experiments demonstrate the production of a human lymphocyte factor (lymphokine) that induces LP synthesis. This pyrogen-inducing lymphokine may be important in the pathogenesis of fever in certain immunologically mediated diseases.
Antigen-specific T lymphocyte clones. I. Characterization of a T lymphocyte clone expressing antigen-specific suppressive activity.
Authors: Fresno M , Nabel G , McVay-Boudreau L , Furthmayer H , Cantor H
Published: June 2004

We have generated continuously propagatable T lymphocyte clones to study antigen-specific T cell functions. All Ly-2+ clones mediate suppressive activity and secrete a characteristic pattern of polypeptides that differs from Ly-2- T cell clones. Cells of one clone, Cl.Ly23/4, specifically bind glycophorin from sheep erythrocytes (SRBC). After incubation with [35S]methionine, supernate material from this clone also contains biosynthetically labeled 70,000-mol wt proteins that specifically bind to SRBC and this binding is inhibited by glycophorin from sheep but not other erythrocytes. These antigen-binding 70,000-mol wt peptides specifically and completely suppress primary anti-SRBC responses generated by mixtures of primed Ly-1+2- cells and B cells. Suppression by these antigen-binding peptides reflects direct inhibition of T-helper activity.
Loss of an individual idiotype on chemical modification. A strategy for assigning idiotypic determinants.
Authors: Dickerman J , Clevinger B , Friedenson B
Published: June 2004

Two dextran-binding myeloma proteins, J558 and Hdex 24, which possess the same individual idiotype (IdI) were diazotized to low levels (1-3.3 groups per subunit) with 1-[14C]-p-aminobenzoate. Both proteins lost the IdI idiotype under these conditions with most of the label incorporated on the heavy chains of each protein. When the diazotization ws carried out in the presence of the hapten 1-O-methyl-alpha-D-glucopyranoside the loss of idiotypic reactivity could be prevented for J558 but not for Hdex 24. Under these conditions most of the label was incorporated on the light chains of J558, but on the heavy chains of Hdex 24. For J558, these results show that a major determinant of the individual idiotype is within the hypervariable positions of the heavy chain. For Hdex 24 the determinant being modified is on the heavy chain but not involved in hapten binding. These results are consistent with previous work showing that J558 and Hdex 24 differ in amino acid sequence in the D and the J segments of the heavy chain and offer an alternative and complementary strategy for assigning idiotypic determinants.
Self recognition in allogeneic radiation bone marrow chimeras. A radiation- resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells
Authors: Singer A , Hathcock KS , Hodes RJ
Published: June 2004

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants.

Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.
Isolation of plasma membrane from human neutrophils and determination of cytochrome b and quinone content
Authors: Sloan EP , Crawford DR , Schneider DL
Published: June 2004

Analyses of plasma membrane and other subcellular fractions indicate that the primary location of cytochrome b in human neutrophils is not the plasma membrane. The procedure developed for the purification of plasma membrane from fresh human neutrophils yielded a 14-fold enrichment in the marker enzyme 5'-nucleotidase and a 10-fold enrichment in ouabain-sensitive ATPase. On sucrose density gradients, the peak density of 5'-nucleotidase activity was 1.12 g/ml, and was shifted after digitonin addition to 1.15 g/ml. Protein in the plasma membrane equalled approximately 8 percent of the whole cell protein.

A b-type cytochrome was found to be present in the plasma membrane fraction at a concentration of 205 pmol/mg of protein, which is three times greater than that in the neutrophil overall. Although this cytochrome has been reported previously in the neutrophil, this is the first determination for purified plasma membrane and may indicate that b-type cytochrome has a dual localization in the human neutrophil. Differential centrifugation results suggest that the primary location is in the granules, probably specific granules.

Quinone content in the plasma membrane was found to be 740 pmol/mg of protein, a concentration two times greater than in the whole cell. Such a small enhancement of quinone indicates that quinone also is not primarily located in the plasma membrane.
Heterogeneity of tumorigenicity phenotype in murine tumors. I. Characterization of regressor and progressor clones isolated from a nonmutagenized ultraviolet regressor tumor
Authors: Schmitt M , Daynes RA
Published: June 2004

We have shown that both regressor and progressor clones can be isolated from a UV regressor tumor, RD-1024. Although the daughter clones are characterized by differences in tumorigenic potential in normal transplant hosts, they nevertheless seem to express the same major tumor rejection antigens, because immunization with either the regressor parent tumor, RD-1024, or with regressor Cl 8 protects against subsequent challenge with progressor C1 4 or Cl 9. Consistent with the in vivo-generated data is the evidence that draining lymph node cells with functional specificity for regressor Cl 8 are capable of cross-reactive cytotoxicity in an in vitro chromium release assay.

We have demonstrated an indirect interaction occurring in vivo between regressor and progressor cells, in that Cl 8 cells have the ability to influence the outcome of simultaneous or sequential challenge with Cl 4 or Cl 9 cells. Because 500 rad of gamma irradiation has been shown to compromise the ability of mice to respond to a primary challenge with tumor, an immunological mechanism is implicated in the ultimate rejection of progressor tumor in a doubly challenged host.

The importance of these results lies in the knowledge that these interacting subpopulations have been isolated directly from a tumor growing in vivo and that no selection pressure has been exerted on the cells greater than the short in vitro culture period necessary for the isolation and expansion of individual clones. The apparent immunoregulatory potential in a tumor-bearing animal is thus seen to be modified in accordance with the phenotypic heterogeneity of the cells within that tumor.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. IX. Characterization of Idiotype-specific effector-phase suppressor cells on plaque-forming cell responses in vitro.
Authors: Sherr D H , Dorf M E
Published: June 2004

The ability of T suppressor cells, induced by the intravenous injection of 4-hydroxy-3-nitrophenyl acetyl (NP)-modified syngeneic spleen cells, to affect an ongoing B cell response was studied in vitro. It was found that the expression of NPb idiotype-positive B cells could be selectively inhibited by the addition of antigen-induced suppressor cells in the last 24 h of the in vitro culture. This effector-phase suppression of B cell responses was antigen specific and mediated by an Lyt 1-, Lyt 2+, idiotype-binding, T cell population whose suppressive function was restricted by genes linked to the Igh locus.
The glycoprotein isolated from vesicular stomatitis virus is mitogenic for mouse B lymphocytes.
Authors: Goodman-Snitkoff G , Mannino R J , McSharry J J
Published: June 2004

The glycoprotein (G protein) of VSV was purified from the intact virion by Triton X-100 extraction. The isolated G protein has been shown to be a T cell-independent, B lymphocyte mitogen and polyclonal activator. Neither G protein nor the intact virion are stimulatory for murine T lymphocytes. The greater the density of G protein in lipid vesicles or the degree of aggregation of isolated G protein, the more highly stimulatory it is for murine splenocytes. As G protein is spread out in artificial vesicles, it becomes less mitogenic. It is probable that other viral components are also stimulatory since the Triton-insoluble pellet and VSV from which the G protein has been enzymatically removed retain mitogenic activity. To out knowledge, this is the first time a purified viral component has been demonstrated to be lymphocyte mitogen.
Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity.
Authors: Ledbetter J A , Seaman W E , Tsu T T , Herzenberg L A
Published: June 2004

Lyt-2 and Lyt-3 antigens are carried on separate disulfide-bonded subunits of the same cell surface macromolecules. These are present on thymocytes in a variety of multimeric forms consisting of disulfide-bonded dimers, tetramers, and hexamers of pairwise combinations of three subunits (30,000, 34,000, and 38,000 Mr). From reduced and alkylated Nonidet-P40 thymus extracts, a monoclonal anti-Lyt-3 precipitates only the 30,000 Mr subunit, but not the 30,000 Mr subunit. Almost all of the Lyt-2 and Lyt-3 subunits on the cell are covalently linked by disulfide bonds. However, small amounts of free Lyt-3 subunit was seen in some experiments. Similarly, small amounts of Lyt-2-3- material, consisting of dimers of the 38,000 and 34,000 Mr subunits were identified. Each of the three subunits migrated with a basic charge (pI greater than 8) on two-dimensional gels. Cytotoxic effector cells that are blocked by anti-Lyt-2 and anti-3 can be treated with trypsin and other arginine-specific proteases to remove these antigens. At low concentrations of these proteases, Lyt-3 antigens are selectively removed. After selective removal of Lyt-3 antigens, cytotoxic effector cells are still active and blocking of activity by anti-Lyt-3 is significantly reduced, whereas blocking of activity by anti-Lyt-2 is significantly increased. Neither Lyt-2 nor Lyt-3 is allelically excluded on thymocytes or T cells. These results suggested that the Lyt-2, Lyt-3 macromolecules are associated with but do not serve as the T cell antigen receptor.
Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit.
Authors: Yamauchi K , Green D R , Eardley D D , Murphy D B , Gershon R K
Published: June 2004

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly-2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.
Presence of interchain disulfide bonds between two gene products that compose the secreted form of an antigen-specific suppressor factor.
Authors: Taniguchi M , Saito T , Takei I , Tokuhisa T
Published: June 2004

The secreted form of the suppressor T cell factor specific for keyhole limpet hemocyanin derived from the hybridoma 34S-704 was found to consist of the two distinct polypeptide chains, i.e., the antigen-binding and the I-J-encoded chains. They were linked in covalent association with disulfide bonds. The two chains were cleaved by the reduction with dithiothreitol and were easy to reconstitute the active form of TsF. The association of the two distinct chains was suggested to be essential for the expression of the TsF activity.
Phorbol myristate acetate stimulates phagosome-lysosome fusion in mouse macrophages.
Authors: Kielian M C , Cohn Z A
Published: June 2004

The effect of the tumor promoter phorbol myristate acetate (PMA) on phagosome-lysosome (P-L) fusion in mouse macrophages has been studied using a previously described (10) fluorescence assay. Treatment with 0.1--1.0 microgram PMA/ml caused a striking increase in the rate and extent of P-L fusion. Exposure of cells to phorbol, free myristate, or the monoesters of PMA did not reproduce this effect. Macrophages required from 2 to 3 h of pretreatment to express maximal P-L fusion, and this was maintained for at least 20 h when cells were returned to PMA-free medium. Catalase, superoxide dismutase, indomethacin, and hydrocortisone, agents that are known to block the effect of PMA on H2O2, O2-, prostaglandins, or plasminogen activator, did not affect the stimulation of P-L fusion by PMA. The protein-synthesis inhibitors puromycin and cycloheximide did block the PMA effect under conditions in which the high fusion rate of 4-d cells was not affected. Labeled PMA was rapidly taken up by macrophages, with a plateau of uptake at approximately 3 h. When cells were returned to PMA-free medium, cel-associated label was rapidly released, returning to background level within 1 h. The released label was found to be a metabolite of PMA by thin-layer chromatography. This product migrated between the monoester phorbol-12-myristate and free phorbol. Rapid metabolism of PMA was also observed by a macrophage cell line, J774, and, to a lesser extent, by primary rat embryo fibroblasts.
Immunoregulatory changes induced by total lymphoid irradiation. II. Development of thymus-leukemia antigen-positive and -negative suppressor T cells that differ in their regulatory function.
Authors: King D P , Strober S
Published: June 2004

BALB/c mice treated with total lymphoid irradiation (TLI) develop non-antigen-specific suppressor cells of the adoptive secondary antibody response and of the mixed leukocyte reaction. Suppressors of the adoptive anti-DNP response were eliminated by incubation of spleen cells with anti-Thy-1.2 or anti-thymus-leukemia (TL) antiserum and complement before cell transfer. Thymectomy before TLI prevented the appearance of the latter suppressor cells. On the other hand, suppressors of the MLR were eliminated by incubation of spleen cells with anti-Thy-1.2 but not anti-TL antiserum and complement. Thymectomy before TLI did not prevent their subsequent development. Thus, two subpopulations of suppressor T cells that differ in the expression of the TL surface antigen, dependence on the presence of the thymus, and in regulatory functions develop after TLI. The TL+, thymus-dependent cell suppresses the adoptive antibody response, and the TL-, thymus-independent cell suppresses the MLR.
Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus.
Authors: Lazure C , Hum W T , Gibson D M
Published: June 2004

We previously showed that a chromosome 6 locus, IgK-Ef2, controls a pair of prominent bands in normal mouse light-chain isoelectric focusing profiles. Screening of myeloma light chains derived from BALB/c mice (an IgK-EF2 alpha strain) led to the identification of seven light chains cofocusing with the polymorphic bands controlled by IgK-Ef2. Complete sequencing of the variable (V) regions of four of the light chains indicates that they are all members of the same subgroup (Vk-1A) and they differ from one another by 1--3 substitutions. One of the protein differs from the prototype V-region sequence only in the deletion of a single residue at position 95 immediately preceding of J region. The other two differ from the protype V region by 3 (two framework [fr], one complementarity-determined [cdr]) and one (fr) residues, respectively. Complete V-region sequences of two closely related light chains derived from NZB mice (an IgK-Ef2b strain) indicate the NZB proteins are derived from a distinct Vk gene (Vk-1B), differing by four substitutions from the Vk-1A sequence. The results suggest that the IgK-Ef2 polymorphism may be a result of, at least in part, the loss of the gene(s) coding for the Vk-1A subgroups in IgK-Ef2b strains of mice. The nature of the sequence diversity found in the Vk-1A subgroup indicates that either it is coded by a repeated series of virtually identical genes or that somatic mutation of a single Vk-1A gene may give rise to substitutions in framework as well as cdr regions.
Characterization of a soluble suppressor of human B cell immunoglobulin biosynthesis produced by a continuous human suppressor T cell line.
Authors: Fleisher T A , Greene W C , Uchiyama T , Goldman C K , Nelson D L , Blaese R M , Waldmann T A
Published: June 2004

A human suppressor T cell maintained in long-term culture with conditioned medium containing interleukin 2 elaborates a suppressor factor(s) that specifically inhibits human polyclonal B cell immunoglobulin biosynthesis. This soluble immune suppressor supernate of immunoglobulin production (CTC-SISS-B) shares a number of features with the previously described suppressive mediator elaborated by concanavalin A-activated human peripheral T cells (SISS-B) including: (a) the inhibition by a noncytotoxic mechanism, (b) the suppression of immunoglobulin biosynthesis either through direct action on the B cell or indirect action via the monocyte, (c) the loss of inhibition in the presence of the monosaccharide L-rhamnose, (d) the elaboration by cells irradiated with 500 ro 2,000 rad, and (e) molecular weights of 60,000--90,000. Furthermore, the suppression by this mediator appears to be specific for B cell immunoglobulin production in that CTC-SISS B has no effect on T cell proliferation to mitogens, antigens, an allogeneic cells or on T cell-mediated cytotoxicity. These data indicate that one possible mechanism of suppressor T cell inhibition of human immunoglobulin production is via the generation of a lectinlike suppressor lymphokine that interacts with defined saccharide determinants on the cell surface of either the B cell or monocyte.
Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus.
Authors: Haller O , Arnheiter H , Gresser I , Lindenmann J
Published: June 2004

The efficacy of interferon in antiviral protection of newborn mice differing at the Mx locus was investigated. Adult mice bearing the allele Mx exhibit a high degree of specific resistance toward lethal challenge with influenza viruses. In contrast, newborn Mx carriers are virtually as susceptible to influenza viruses as newborn mice devoid of Mx. Resistance can be abrogated by treating adult animals with anti-interferon serum. Here, we provide direct evidence of a virus-specific effect of interferon in vivo: newborn mice carrying the resistance gene Mx could be protected against lethal influenza virus infection with doses of interferon that were not protective in the absence of Mx. The efficacy of interferon towards a picornavirus (encephalomyocarditis virus) and a rhabdovirus (vesicular stomatitis virus) was independent of Mx.
(NZW x BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction.
Authors: Hang L M , Izui S , Dixon F J
Published: June 2004

Both sexes of the (NZW x BXSB)F1 mice developed an early systemic lupus erythematosus-like disease. In males, the disease resembled that in the BXSB male parent and was not affected by sex hormonal manipulation. In females, the disease duplicated that of (NZB x NZW)F1 females by virtue of a delayed onset and estrogen dependence. Autoantibody production, circulating Ig-bound gp 70 immune complexes, and deposition of Ig and gp 70 in the affected glomeruli were demonstrated in both males and females. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction, particularly in these F1 males, provides a useful model for the investigation of a possible immunologic component in coronary vascular disease.
Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells
Authors: Sorensen CM , Pierce CW
Published: June 2004

C57BL/10 mice were injected with semiallogeneic (B10.D2 X C57BL/10)F(1) spleen cells via the anterior facial vein within 24 h of birth to induce tolerance to B10.D2 (H-2(d)) alloantigens. Spleen cells from these mice as adults developed reduced, but significant, mixed lymphocyte and cytotoxic lymphocyte responses in vitro to H-2(d) stimulator cells and these treated mice rejected first-set B10.D2 skin grafts within a normal time-course, indicating that at best only a state of partial tolerance had been induced. Spleen cells from these mice failed to develop antibody responses to a variety of antigens in vitro when H-2(d) macrophages were in the cultures. Partially purified T cells from these neonatally treated mice suppressed primary antibody responses by normal syngeneic spleen cells in the presence of H-2(d) but not other allogeneic macrophages. These radiosensitive, haplotype-specific suppressor T (Ts) cells inhibited primary antibody responses by blocking initiation of the response, but failed to suppress secondary antibody responses and mixed lymphocyte or cytotoxic lymphocyte responses by appropriate responding spleen cells. To activate H-2(d) haplotype-specific Ts cells, stimulation with IA(d) subregion antigen(s) was necessary and sufficient; syngenicity at the I-A subregion of H-2 between the activated Ts cells and target responding spleen cell populations was also necessary and sufficient to achieve suppression. Comparable results have been obtained with spleen cells from BALB/c mice injected as neonates with (B10.D2 × C57BL/10)F(1) spleen cells where IA(b) antigens activate the haplotype-specific Ts cells. Implications for the significance of this population of haplotype-specific Ts cells in immune regulation are discussed and the properties of these Ts cells are compared and contrasted with other antigen-specific and nonspecific Ts cells whose activity is restricted by I- region products.
Specificity of fc receptors for IgG2a, IgG1/IgG2b, and IgE on rat macrophages.
Authors: Boltz-Nitulescu G , Bazin H , Spiegelberg H L
Published: June 2004

To characterize the Fc receptors on rat alveolar and peritoneal macrophages (M phi), we analyzed their ability to form rosettes with fixed ox erythrocytes (Eo') coated with myeloma proteins of all rat Ig classes and with fresh erythrocytes (Eo) sensitized with rat IgG1 and IgG2, rabbit IgG and IgM, and mouse IgA antibodies. The M phi formed rosettes with Eo' coated with rat myeloma proteins of classes IgG1, IgG2a, IgG2b, and IgE but not IgG2c, IgA, IgM, and IgD. Rat M phi also formed rosettes with Eo' coated with human IgG1, IgG3, IgG4, mouse IgG1, IgG2a, IgG2b, and rabbit IgG. Furthermore, rat M phi formed rosettes with Eo sensitized with rat IgG1, IgG2, or rabbit IgG antibodies but not with Eo sensitized with rabbit IgM or mouse IgA antibodies. Trypsin treatment of rat M phi abolished IgG1/IgG2b and IgE but not IgG2a rosettes. The IgG2a and IgE rosettes were Ig class specific because they were inhibited only by rat IgG2a and rat IgE, respectively. In contrast, IgG1 and IgG2b rosettes were inhibited equally by IgG1 and IgG2b. Heterologous IgG inhibited IgG1/IgG2b but not IgG2a rosettes. Rat IgE inhibited rat IgG1, IgG2b, and heterologous IgG rosette formation on rat M phi. Although Eo' coated with rat IgE formed rosettes with mouse P388D1 macrophagelike cells, rat IgE did not inhibit IgG rosettes on these cells. Similarly, Eo' coated with human IgE formed rosettes with human U937 macrophage-like cells, but human IgE did not inhibit IgG rosettes on these cells. The results indicate that rat M phi have at least three distinct Fc receptors: one is specific for rat IgG2a and is trypsin resistant; a second is specific for rat IgE and is trypsin sensitive; and a third reacts with rat IgG1 rat IgG2b, and heterologous IgG and is trypsin sensitive. Rat IgE inhibited IgG1/IgG2b rosettes undirectionally and uniquely on rat M phi.
Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.
Authors: Thomas Y , Rogozinski L , Irigoyen O H , Friedman S M , Kung P C , Goldstein G , Chess L
Published: June 2004

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XI. Pseudogenetic restrictions of hybridoma suppressor factors
Authors: Okuda K , Minami M , Sherr DH , Dorf ME
Published: June 2004

Suppressor factor derived from three different murine T cell hybridomas were characterized . They specifically inhibited 4-hydroxy-3-nitrophenyl acetyl cutaneous sensitivity responses. The factors bind antigen and bear I-J and idiotypic determinants, but lack conventional immunoglobulin constant-region determinants. The factors function during the induction phase of the immune response, by inducing a second population of suppressor cells (Ts(e)). Suppressor factor can inhibit both cellular and plaque-forming cell responses in appropriate strains of mice. These hybridoma suppressor factors directly suppress strains of mice that are Igh-V homologous with the strain producing the factor. Thus, there is an apparent Igh-V restriction in the activity of these factors. However, this is a pseudogenetic restriction because these factors generate second order suppressor cells (Ts(e)) in Igh-incompatible mice, but in order to express the suppressive activity, the cells must be adoptively transferred into recipients that are Igh compatible with the strain producing the suppressor factor. Finally, it was shown that the factor-induced Ts(e) population is under an apparent dual genetic restriction. Thus, Igh and H-2 homology is required in order for the Ts(e) population to express its suppressive activity.
T lymphocytes specific for immunoglobulin allotype. I. Igh- 1(b)-specific T cells demonstrated by suppression in vivo and cytotoxicity in vitro
Authors: Snodgrass HR , Wilson DB , Bosma MJ
Published: June 2004

We show that determinants of IgG(2a) of C57BL/6 mice (Igh-1(b)) stimulate allotypespecific T cells in BALB/c mice. Such cells are detected in two different functional assays; chronic allotype suppression and T cell-mediated cytotoxicity. A population of suppressor T cells capable of inducing chronic Igh-1(b) suppression was demonstrated by rosetting procedures to possess Igh-1(b)-specific receptors, a result interpreted as indicating that suppressor T cells may act directly upon allotype-bearing B cells. From similar populations we were also able to demonstrate Igh-1(b)-specific cytotoxic T cells. Such cells were lytic for target myeloma cells expressing the Igh-1(b) allotype of IgG28, and were ineffective against a variant cell line failing to express Igh-1(b), and other target cell lines expressing different allotypes or isotypes. The similar specificity of suppressor T cells and cytotoxic T lymphocytes for Igh-1(b) allotype raises the possibility that the target in allotype suppression is a B cell, and that allotype-specific cytotoxic T cells may play some role in regulation of allotype expression in the suppressed state.
T lymphocytes specific for immunoglobulin allotype. II. Cloned Igh-1(b)- specific cytotoxic T cells
Authors: Snodgrass HR , Bosma MJ , Wilson DB
Published: June 2004

This study describes long-term-cultured lines and clones of cytotoxic T cells (Tc) with specificity for determinants of the Igh-1(b) immunoglobulin allotype. These Tc clones were initiated by repeated stimulation of immune spleen cells from BALB/c mice with an Igh-1(b)-producing myeloma, and then they were maintained in medium supplemented with mitogen-induced growth factors in the absence offurther antigenic stimulation . The lytic potency of these clones was 30-100-fold greater than the primary cultures from which they were derived, and specificity studies showed them to be lytic for Igh-1(b) targets and not for targets expressing Igh-1(a) or Igh-4(b), nor the lipopolysaccharide blasts . Finally, soluble preparations of Ig were tested for their ability to block lysis of labeled Igh-1(b)-expressing targets. The results showed that Igh-1(b) and not other immunoglobulin allotypes or isotypes could block lysis, and that the mechanism of lytic inhibition is due to Igh-1(b)-induced autolysis of the killer cells.
Surface markers of cloned human T cells with various cytolytic activities.
Authors: Moretta L , Mingari M C , Sekaly P R , Moretta A , Chapuis B , Cerottini J C
Published: June 2004

Human T cells stimulated in secondary allogeneic mixed lymphocyte culture (MLC) were cloned under limiting conditions in microculture systems using T cell growth factor and irradiated allogeneic cells. Clones with lytic activity against either phytohemagglutinin-induced blast cells bearing the stimulating alloantigen(s) (cytotoxic T lymphocyte [CTL] activity), L1210 mouse lymphoma cells coated with rabbit antibody (antibody-dependent cell-mediated cytotoxicity [ADCC]), or K562 human target cells were selected, expanded, and then analyzed for different surface markers, including rosette formation with sheep erythrocytes (E rosettes), receptors for the fc portion of IgG or IgM (Fc gamma R and Fc mu R), and a group of antigens recognized by monoclonal antibodies including Ia, 4F2, OKT8,a nd OKT4. All the cytotoxic cells were E rosette+, Ia+ and 4f2+. Expression of Fc gamma R was restricted to the clones active in ADCC. CTL clones were either OKT8+ or OKT8-. Furthermore, three of the OKT8- CTL clones were OKT4+. In addition, some cytolytic clones devoid of specific CTL activity were OKT8+. It thus appears that the claim that human CTL are OKT8+, OKT4-, and Ia- is not supported by the analysis of their phenotype at the clonal level.
Mechanisms of anti-tumor action of Corynebacterium parvum. I. Potentiated tumor-specific immunity and its therapeutic limitations.
Authors: Dye E S , North R J , Mills C D
Published: June 2004

The anti-tumor mechanism in mice induced by a subcutaneous injection of syngeneic tumor cells admixed with Corynebacterium parvum was investigated. When mice were implanted in a hind footpad with x 2 1096) tumor cells admixed with 100 microgram C. parvum, the tumor that emerged grew progressively for about 9 d and then underwent progressive and complete regression. It was found that this C. parvum-induced regression was associated with the acquisition of a systemic, T cell-mediated mechanism of immunity to tumor-specific transplantation antigens, which enabled the host to cause the regression of an untreated test tumor growing simultaneously at a distant site. The generation of a C. parvum-potentiated anti-tumor response was dependent on the presence of tumor cells in close association with C. parvum, tumor immunogenicity, and the quantity of tumor antigen in the admixture. The anti-tumor immunity was specific for the tumor in the therapeutic admixture and could be adoptively transferred to normal recipients with Thy-1.2-positive lymphocytes, but not with serum. Complete regression of a distant test tumor by the C. parvum-tumor admixture was limited to tumors below a certain critical size.
Mechanisms of anti-tumor action of Corynebacterium parvum. II. Potentiated cytolytic T cell response and its tumor-induced suppression.
Authors: Mills C D , North R J , Dye E S
Published: June 2004

It was shown that subcutaneous implantation of P815 tumor cells admixed with Corynebacterium parvum resulted in the emergence of a tumor that grew for 9-10 d and then regressed. The onset of tumor aggression was preceded by the substantial generation in the draining lymph node and spleen of T cells capable of specifically lysing P815 target cells in vitro. The finding that the magnitude of this cytolytic response was much greater than the cytolytic response to a control tumor that grew progressively is consistent with the hypothesis that the anti-tumor action of C. parvum is based on its capacity to augment the production of T cells sensitized to tumor-specific transplantation antigens. This adjuvant action of C. parvum was revealed by additional experiments in which irradiated, nonreplicating tumor cells were substituted for living tumor cells in the admixture. The results support the conclusion that the potentiated cytolytic response to subcutaneous injection of an admixture of irradiated tumor cells and C. parvum is responsible for the ability of this admixture to cause the regression of a test tumor growing at a distant site. Finally, it was shown that the failure of the therapeutic admixture to cause the regression of distant test tumors above a certain size was associated with a failure of the admixture to cause a potentiated, anti-tumor cytolytic response. We discussed the possibility that this failure was caused by the presence of a tumor-induced state of immunosuppression.
The expression of anti-poly(LGlu60, LPhe40) idiotypic determinants dictated by the gene products in the major histocompatibility complex.
Authors: Babu U M , Maurer P H
Published: June 2004

Antibodies raised in SWR/J mice (H-2q, Igc) to the random copolymer poly(LGlu60, LPhe40) (GPhe) were purified by immunoadsorbent chromatography and used to immunize a New Zealand red rabbit. The rabbit anti-idiotypic antiserum thus produced strongly inhibited the binding of 125I-GPhe by anti-GPhe antisera produced only in mice of H-2q haplotype, and had no effect on the binding of GPhe by anti-GPhe antisera produced in mice of other haplotypes, namely, H-2k and H-2p. The anti-idiotypic antiserum also inhibited the binding of GPhe by anti-GPhe-methylated bovine serum albumin antisera produced only in mice of H-2q haplotype. No linkage to Ig allotype was observed. The anti-GPhe antisera produced in F1 mice the anti-idiotypic antiserum demonstrating the dominant presence in these F1 mice of idiotypic determinants whose expression is dictated by the H-2q major histocompatibility complex (MHC). The anti-idiotypic antiserum also inhibited the binding of 125I-poly)LGlu56, LLys35, LPhe9) and 125I-GPhe antisera produced only in mice of H-2q haplotype. These specificities were also confirmed by the inhibition of the plaque-forming cells. It was concluded that the antibodies produced in mice of H-2q haplotype against GPhe and GLPhe share common idiotypic determinants that are recognized by the anti-idiotypic antiserum. A possible explanation for the unique findings that the expression of anti-GPhe idiotypic determinants in mice of H-2q haplotype are dictated by the gene product in the MHC is that the macrophages in mice of H-2q haplotype present unique determinants of GPhe polymer in the response process to GHphe.