bluuebunny/crossref_metadata_2025 huggingface dataset:
Bile pigment formation by skin heme oxygenase: studies on the response of the enzyme to heme compounds and tissue injury.
Authors: Maines M D , Cohn J
Published: June 2004

Skin heme oxygenase is locally elevated by stimuli such as tissue injury and injections of whole blood, myoglobin, and hematin. The enzyme activity is also increased at the proximity of the injection site of chemicals such as cobalt and cobalt-protoporphyrin-IX (cobalt-heme). Protoporphyrin-IX, the tetrapyrrole nucleus of type-b heme compounds, was ineffective in altering the enzyme activity in vivo. The developmental pattern of heme oxygenase in skin was compared to that of the enzyme in liver. The enzyme activity in both organs was greatest during the 1st postpartum wk and declined to adult levels after 2 wk. The physiological implications of the increased activity of skin heme oxygenase are discussed, and it is concluded that the activity of the hepatic heme oxygenase system and that of the skin are regulated by the same mechanism.
T-T interactions in the induction of suppressor and helper T cells: analysis of membrane phenotype of precursor and amplifier cells.
Authors: Feldmann M , Beverley P C , Woody J , McKenzie I F
Published: June 2004

The Ly and Ia phenotypes of T lymphocytes involved in the in vitro generation of helper and suppressor cells were identified. The precursors of both cells are found in adult thymectomized spleen. Helper precursors are Ly-1+2-3-Ia-, while suppressor precursors are Ly-1-2+3+Ia-, although the suppressor effector is Ia+. In both cases a second 'amplifier' cell is required for differentiation of precursors to occur. This cell is found in anti-lymphocyte serum-treated spleen and has the phenotype Ly-1+2+3+Ia-.
Estrogen binding by leukocytes during phagocytosis,.
Authors: Klebanoff S J
Published: June 2004

Estradiol binds covalently to normal leukocytes during phagocytosis. The binding involves three cell types, neutrophils, eosinophils, and monocytes and at least two reaction mechanisms, one involving the peroxidase of neutrophils and monocytes (myeloperoxidase [MPO]) and possibly the eosinophil peroxidase, and the second involving catalase. Binding is markedly reduced when leukocytes from patients with chronic granulomatous disease (CGD), severe leukocytic glucose 6-phosphate dehydrogenase deficiency, and familial lipochrome histiocytosis are employed and two populations of neutrophils, one which binds estradiol and one which does not, can be demonstrated in the blood of a CGD carrier. Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD. These findings are discussed in relation to the inactivation of estrogens during infection and the possible role of estrogens in neutrophil function.
Recirculating, suppressor T cells in transplantation tolerance.
Authors: Dorsch S , Roser R
Published: June 2004

An adoptive transfer system was used to examine the capacity of cellular inocula from rats fully tolerant of Ag-B antigens to transfer tolerance to irradiated recipients. Permanent tolerance in these irradiated recipients involved specific suppression of the regenerating immune response. Cells obtained from tissues rich in recirculating lymphocytes were the most effective suppressors. Highly purified inocula of T cells from tolerant donors were potent suppressors in irradiated hosts, but were not capable of direct suppression of peripheral antigen-sensitive T cells.. The role of the thymus in maintaining the complement of recirculating suppressor T cells in tolerant animals was examined after adult thymectomy. Thymectomized tolerant rats did not reject their tolerated grafts, and the longevity of the suppression in tolerant rats was confirmed by showing that adoptive transfer of cells from thymectomized tolerant donors was effective in suppressing irradiated recipients up to 180 days after thymectomy. Cellular inocula from these donors appeared to lose their suppressor function marginally faster than they lost effector function (as measured by their capacity to mediate rejection of third party control grafts). Thymectomy made tolerant rats more vulnerable to the termination of tolerance by challenge with normal cells. Transplantation tolerance is maintained in adult rats by long-lived rapidly recirculating suppressor T cells. The target for the suppressor action of these cells is probably the precursor of alloantigen-sensitive lymphocytes, and the effect of suppression may be deletion or inactivation of the relevant clone of these cells.
Immunological studies of Aging. III. Cytokinetic basis for the impaired response of lymphocytes from aged humans to plant lectins.
Authors: Inkeles B , Innes J B , Kuntz M M , Kadish A S , Weksler M E
Published: June 2004

The basis for the age-associated defect in the response of lymphocytes to plant lectins has been studied. Using three independent assays we have shown that the number of mitogen-responsive cells is markedly reduced in lymphocyte preparations from old persons. In addition, studies using colchicine bloock and thymidine pulse techniques have revealed a failure of mitogen-responsive cells from old persons to expand into a proliferating pool of lymphocytes as is observed when lymphocytes from young persons are cultured with phytohemagglutinin. Thus, the impaired response of lymphocytes from old persons to mitogens is attributable to a reduced number of mitogen responsive cells and their failure to undergo clonal expansion.
Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide.
Authors: Esquivel P S , Rose N R , Kong Y C
Published: June 2004

The administration of soluble mouse thyroglobulin (MTg) in conjunction with bacterial lipopolysaccharide (LPS) led to the termination of natural tolerance to MTg in mice. The extent of autoimmunity correlated with responsiveness to MTg, previously shown by the injection of MTg in complete Freund's adjuvant (CFA) to be dependent upon the H-2 haplotype. In good responder B10.BR (H-2k) mice given MTg either with LPS or in CFA, high antibody levels to MTg and extensive mononuclear cell infiltration in the thyroid were observed. In contrast, congenic poor responder B10.D2 (H-2d) mice given MTg plus LPS showed low levels of antibody to MTg, compared to those receiving MTg in CFA, and insignificant cellular infiltration of the thyroid. In no instance did autoimmunity develop in either good or poor responder strain given MTg, LPS, or CFA along although LPS was antigenic in both of these congenic strains. Since the genetic difference in responsiveness to MTg is known to be T-cell based, the involvement of T cells in LPS-treated mice was suspected. This was further ascertained by the use of athymic poor responder (BALB/c) mice and thymectomized, irradiated, and bone marrow-reconstituted B10.BR mice. Antibodies to MTg were detected only in heterozygous (nu/+) mice and good responder mice reconstituted with both thymus and bone marrow cells. In addition, significant cellular infiltration in the thyroid occurred only in fully reconstituted good responder mice. Thus, the adjuvant effect of LPS on responsiveness to MTg required T cells. Since unmodified MTg and LPS abrogated selftolerance to MTg, the need for cross-reactive T cells could be excluded. These observations suggest the presence of self-reactive T cells.
Receptors for IgG: subclass specificity of receptors on different mouse cell types and the definition of two distinct receptors on a macrophage cell line.
Authors: Heusser C H , Anderson C L , Grey H M
Published: June 2004

To evaluate subclass specificity and aggregate size requirements of IgG receptors on mouse cells, we measured binding of radiolabeled monomeric and BDB-aggregated mouse myeloma proteins fractionated into various sizes by means of gel filtration. Monomers, tetramers, and high molecular weight (approximately 10(7) daltons) aggregates were used. The various cells and cell lines studied could be segregated into three patterns of reactivity: (a) Macrophage and macrophage-like cell lines bound monomer IgG2a preferentially; high molecular weight IgG aggregates bound as follows: IgG1 = IgG2b = IgG2a. (b) Lymphoid lines D2N and S49 showed no capacity to bind monomer IgG2a; high molecular weight aggregates bound as follows: IgG1 = IgG2b less than IgG2a. (c) Other Thy-1-positive lymphoid cell lines (EL4 and L5178) and normal T and B cells showed no capacity to bind monomer IgG; high molecular weight IgG aggregates bound to a lesser extent than to cells of the first two categories in the following manner: IgG1 less than IgG2b greater than or equal to IgG2a. The variable pattern of reactivity of the macrophage-like cell lines with monomer and aggregated IgG suggested that two distinct receptors for IgG were present: one capable of binding IgG2a and another capable of binding all aggregates. Further evidence for this hypothesis was obtained by analysis of the inhibitory capacity of different IgG subclasses on the binding of aggregated IgG and monomer IgG2a to P388 cells. Inhibition of monomer IgG2a binding was effected only by monomer or aggregated IgG2a, whereas inhibition of binding of aggregated IgG1 or IgG2b was noted with aggregates of all three subclasses with some preferential inhibition by monomer IgG2b being observed. Furthermore, monomer IgG2b binding was preferentially inhibitable by monomer IgG2b. It is postulated from these data that two receptor sites are present on this macrophage-like cell line, one reactive with aggregates of all three subclasses as well as monomer IgG2b, and another receptor specific for monomer IgG2a which also binds aggregated IgG2a. Support of this concept was obtained by trypsinization experiments in which the binding of monomer IgG2a was markedly decreased by trypsin treatment of cells, whereas the binding of aggregated IgG2b was unaffected by this treatment.
The specificity of T-cell helper factor in man
Authors: Geha RS , Mudawwar F , Schneeberger E
Published: June 2004

Supernates of human T cells stimulated with TT antigen contain a factor that induces mitogenesis and immunoglobulin synthesis in autologous as well as allogeneic B cells. A fraction of the IgG produced has specificity against TT. The T-cell-derived LMF-TT eluted after albumin on Sephadex G 200 and did not contain immunoglobulin heavy chain determinants. LMF-TT was active on B cells from TT immune as well as TT- nonimmune individuals but in the latter instance the IgG secreted had no specificity against TT. B cells incubated with LMF-TT in the presence of a second antigen (DT) made IgG with specifity to that antigen provided the B-cell donor was immune to that second antigen.

LMF-TT-containing supernates were depleted of TT antigen by Sephadex G 200 chromatography followed by passage over anti-TT immunosorbent columns. The antigen-free supernates were able to induce mitogenesis and IgG synthesis in B cells but the IgG produced failed to exhibit specificity against TT unless the TT antigen was readded to the B-cell cultures.

The optimal concentration of LMF-TT (50 percent) inducing B-cell mitogenesis was different from the optimal concentration (20 percent) causing IgG synthesis by B cells. At low LMF concentrations (less than or equal 10 percent) addition of a second antigen to which the cell donor was immune caused an increase in the degree of B-cell mitogenesis. Submitogenic concentrations of LMF-TT (less than or equal to 5 percent) were still capable of inducingimmunoglobulin synthesis in B cells At these low concentrations of LMF-TT the proportion of anti-TT IgG over total IgG increased sharply.

B cells from TT immune donors were separated on TT immunosorbent columns. Cells that bound to the column were more sensitive to the mitogenic and IgG synthetic effects of LMF-TT than unfractionated B cells.

Thus, LMF is a nonspecific human T-cell helper factor which behaves like a polyclonal B-cell activator. However, in the presence of specific antigen (TT) the antigen-specific B cell is preferentially triggered by LMF. The experimental design of the present study does not rule out the additional presence of an antigen-specific helper factor in the supernates of TT-stimulated human T cells.
Cultured human monocytes synthesize and secrete alpha2-macroglobulin.
Authors: Hovi T , Mosher D , Vaheri A
Published: June 2004

alpha2-Macroglobulin levels in the supernates of cultures of different subpopulations of human peripheral blood mononuclear leukocytes were assayed by a radioimmunoassay. Unfractionated mononuclear leukocytes produced greater amounts of the macroglobulin (4.0 vs. 0.8 ng/10(6) cells) than did subpopulations enriched in T or B+T lymphocytes, by passage through nylon wool or cotton wool columns, respectively. Still higher concentrations of alpha2-macroglobulin (40 ng/10(6) cells) were measured in the supernates of glass-adherent mononuclear leukocyte cultures. These results suggest that cells of monocyte-macrophage lineage are mainly, if not exclusively, responsible for the appearance of alpha2- macroglobulin in the supernate of human peripheral blood leukocyte cultures. The de novo synthesis and release of alpha2-macroglobulin by cultured monocytes was demonstrated by immunoprecipitation of radioactivity from supernates of 32S-methionine-labeled glass-adherent cells. Antiserum against purified alpha2-macroglobulin was used in both Ouchterlony double diffusion and double antibody precipitation tests. SDS-polyacrylamide gel electrophoresis of immunoprecipitates showed that most of the radioactivity comigrated with authentic alpha2-macroglobulin subunit at about 160,000 daltons.
Carrier-directed anti-hapten responses by b-cell subsets
Authors: Lewis GK , Goodman JW
Published: June 2004

The capacity of the trinitrophenyl (TNP) haptenic group, coupled to a series of chemically dissimilar carriers, to cross-stimulate putative T- dependent and T-independent murine B-cell subpepulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. It was found that TNP-Ficoll and TNP-dextran, two T- independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-bacterial lipopolysaccharide (LPS), a T-independent polyclonal mitogen, or TNP-horse erythrocytes (HRBC), a T-dependent antigen. On the other hand, TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T- cell signal in T-dependent B-cell responses, whereas nonmitogenic T- independent antigens cannot. However, the cumulative evidence from this and other laboratories strongly indicates that LPS and T-dependent antigens activate B cells by different mechanisms. Of particular interest, LPS is incapable of activating B cells responsive to weakly- or nonmitogenic T-independent antigens.

Based on clonal burst size, T-dependent antigens are capable of inducing greater antigen-specific B-cell proliferation than T-independent antigens. However, TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B-cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen.

The findings reinforce the evidence favoring existence of multiple B- cell subpopulations with distinctive activation pathways. They also strengthen the proposition that a given B-cell subset can be activated by more than one mechanism.
Differentiation of memory T cells to virus plaque-forming cells and cytotoxic T lymphocytes
Authors: Senik A , Bloom BR
Published: June 2004

The aims of this study were to define the T-cell subpopulation(s) detected by the virus plaque assay, and particularly to determine whether the virus plaque assay could be used to enumerate cytotoxic T lymphocytes. In addition, studies were undertaken to ascertain whether cell proliferation was required for development of cytotoxic effector function and virus plaque formation by these subpopulations. The results of experiments with a secondary mouse mixed lymphocyte culture (MLC) model indicated that 70 percent of virus plaque-forming cells bore the Ly 1 phenotype and 30 percent the Ly 2,3 phenotype. Three lines of evidence suggested that cytotoxic T lymphocytes (CTL) can be detected by this assay: the fact that some virus plaque-forming cells (V-PFC) bear the same Ly phenotype as CTL; the use of an inhibitor of DNA synthesis indicated that proliferating cells could be eliminated with no effect on V-PFC production and cytotoxic activity of the Ly 2,3 cell population; and that infection of primed lymphocyteswith vesicular stomatitis virus before (MLC) stimulation eliminated cytotoxic activity.

In primary MLC, development of V-PFC and CTL was completely abolished by cytosine arabinoside. In contrast, in secondary MLC, some CTL and V- PFC were generated by antigenic stimulation in the absence of proliferation. However, the development of both functions became progressively more susceptible to cytosine arabinoside as the time between primary immunization and in vitro boosting is increased. It is suggested that there may be a considerable disparity between the number of existing effector cells at any given time and the cytotoxic potential, i.e. the number of cells capable of being generated by antigenic stimulation.
Properties of reticulum cell sarcomas in SJL/J mice. V. Nature of reticulum cell sarcoma surface antigen which induces proliferation of normal SJL/J T cells.
Authors: Ponzio N M , David C S , Shreffler D C , Thorbecke G J
Published: June 2004

The results of studies on the reticulum cell sarcoma (RCS) tumors of SJL/J mice presented here, indicate that spontaneous tumors, which arise in older mice, also possess the capacity to induce the vigorous proliferative response in syngenetic T lymphocytes that are characteristic of the transplantable RCS lines. Analysis of cell surface antigens revealed the presence of Ia determinats on gradient-purified transplantable RCS tumor cells; however, these cells did not express Thy 1.2, nIg, or, any of the viral proteins that were tested for by specific antisera. Pretreatment of RCS cells with anti-Ia sera and complement-deleted cells that were stimulatory for syngenetic T lymphocytes, and addition of anti-Ia sera directly to cultures blocked the proliferative response at the stimulator (RCS) cell level. Lymph node cells from H-2(8) strains other than SJL/J, including A.SW and B10.S also gave proliferative responses to RCS cells, although lower in magnitude. A requirement on the part of responding cells for identity with RCS cells at the Ir region was indicated by the finding that A.TH but not A.TL lymph node cells responded to RCS. It is concluded that RCS cells stimulate Ir-region identical T cells (without evidence of presensitization) through a modification in the expression of Ia antigens on the surface of the tumor cells.
Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development
Authors: Hamaoka T , Yoshizawa M , Yamamoto H , Kuroki M , Kitagawa M
Published: June 2004

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL.

Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL.

Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.
The specific antigen-binding cell populations of individual fetal mouse spleens: repertoire composition, size, and genetic control
Authors: Cohen JE , D'Eustachio P , Edelman GM
Published: June 2004

In order to analyze the genetic and physiological basis of controls affecting the generation of the repertoire of antigen-binding cells in fetal mice, we have measured the numbers of spleen cells specific for each of four antigens as a function of the total numbers of nucleated and Ig-bearing cells in inbred, hybrid, and random bred fetuses. For each of the two inbred strains BALB/c and CBA/J, the proportion of nucleated cells specific for a given antigen was the same for all individuals of the strain at the 18th day of gestation. The proportion did vary from antigen to antigen, however, and for each antigen the proportion of specific cells observed in CBA/J fetuses was approximately four times that observed in BALB/c fetuses. This difference appeared to be due to a difference between the two strains in the relative size of the repertoire of antigen-binding spleen cells at this stage of development, inasmuch as the frequency of Ig-bearing spleen cells in CBA/J fetuses was likewise approximately four times that observed in BALB/c fetuses.

In random bred Swiss-L fetal mice at the 18th day of gestation, the proportion of cells specific for a given antigen varied significantly from one individual to the next. The ratio of proportions of the two antigens observed was constant from individual to individual, however, and this constant ratio differed significantly from the ratio observed for the same two antigens in fetal BALB/c and CBA/J inbred mice. These data suggest that the ontogeny of the repertoire of antigen-binding cells in fetal mice is subject to at least two independent sets of controls, one affecting the relative size of the repertoire in the spleen, and the other affecting the distribution of antigen-binding specificities within that repertoire.

Analysis of repertoire size and composition in the spleens of hybrid fetuses confirmed the observation that the two parameters are controlled independently, and suggested further that the control of repertoire size in these fetuses is due to the action of one or a few closely-linked autosomal Mendelian genes. These data are consistent with models for the origin of antibody diversity in which the genes coding for the full repertoire of antibodies are generated somatically from a small number of germ-line genes early in development and in the absence of any strong positive or negative selection with respect to antigenic specificity.
Generation of cytotoxic effector cells by immunocompetent thymus cell subpopulations.
Authors: Dyminski J W , Smith R T
Published: June 2004

Immunocompetent mouse thymus cell subsets (TH-2) cultured with allogeneic TH-2 cells, required a peripheral lymphoid cell in order to generate specifically cytotoxic T cells (CTL) in vitro. The helper cell is identified as a B cell, and can be supplied either in the mixture of target or responding peripheral cells, or in optimal ratios of 10:1 to 20:1 as nonproliferating cells syngeneic to the responder, when both responder and target are TH-2. Allogeneic helper cells are much less effective. Kinetic studies indicate that helper cell activity involves initial interaction with stimulator cell and is then required throughout the period of generation of cytotoxic lymphocytes. Addition of critical levels of certain IgG preparations, particularly IgG2A appears to support generation of CTL in TH-2/TH-2 cultures but is considerably less effective than intact B cells. Cytotoxicity generated under these conditions has the same genetic requirements for I-region histoincompatibility between stimulator and responder, and for K or D identity of stimulator and target cell, as has been reported for peripheral cell CTL.
Expression of AKR murine leukemia virus gp71-like and BALB(X) gp-71-like antigens in normal mouse tissues in the absence of overt virus expression.
Authors: McClintock P R , Ihle J N , Joseph D R
Published: June 2004

By competition radioimmune assays with antisera against AKR murine leukemia virus (MuLV) gp 71 or antisera against xenotropic virus, and iodinated AKR MuLV gp71 or BALB(X) gp71, antigens serologically indistinguishable from the viral antigens can be detected in tissues of normal mice in the absence of overt virus expression. An antigen serologically indistinguishable from AKR MuLV gp71 can be readily detected in normal bone marrow cells of the common strains of mice including NIH Swiss, 129/J, and SWR/J, as well as in Mus cervicolor and Mus musculus casteneus. In contrast, this antigen is not detected in normal spleen, thymus, lymph nodes, or serum. Similarly, an antigen serologically indistinguishable from BALB(X) gp71 was found in all normal mouse sera examined. This antigen was not present in fetal liver, perfused adult liver, thymus, spleen, lymph nodes, or bone marrow of the mice examined. An equivalent antigen was detected in sera from Mus musculus casteneus but not in sera from Mus cervicolor.
Activation of factor XII by tobacco glycoprotein.
Authors: Becker C G , Dubin T
Published: June 2004

A glycoprotein of mol wt ca. 18,000 daltons isolated from cured tobacco leaves (TGP-L) and from cigarette smoke condensate (TGP-CSC) activated factor XII in normal human plasma in vitro as measured by (a) shortening of the partial thromboplastin time, (b) shortening of the lysis time of euglobulin clots, and (c) generation of kinin activity. These effects were not demonstrable in plasma deficient in factor XII. The capacity of TGP-L and TGP-CSC to activate factor XII was shown to depend on the presence of rutin, a substance chemically similar to quercetin and ellagic acid, which are known activators of factor XII. Rutin and rutin coupled to bovine serum albumin, but not bovine serum albumin alone, were also demonstrated to activate factor XII. The presence in cigarette smoke of material that is both allergenic and capable of activating factor XII of the intrinsic pathway of coagulatin may be important to the pathogenesis of cardiovascular and pulmonary disease associated with cigarette smoking.
Cytotoxic T lymphocytes induced against allogeneic I-region determinants react with Ia molecules on trinitrophenyl-conjugated syngeneic target cells
Authors: Billings P , Burakoff S , Dorf ME , Benacerraf B
Published: June 2004

The major histocompatibility complex codes for determinants which are recognized by and serve as targets for cytolytic T lymphocytes (CTL) (1). Antigens coded for by the K and D loci of the H-2 complex can activate xenogeneic or allogeneic CTL (2,3). In addition, the H-2K or H-2D gene products function as those molecules against which syngeneic CTL responses specific for chemical, viral, and minor H antigens are directed (4-8).

It has recently been shown that Ia determinants can also serve as target antigens for distinct but weaker CTL responses (9-13). Those clones which recognize Ia antigens see them independently of K- or D- coded antigens as shown in genetic studies and by antisera-blocking experiments (12,13). We have proposed that the existence of clones of CTL specific for I-region-coded determinants is not fortuitous; rather these clones specifically recognize Ia determinants and may have an immunoregulatory role. These CTL may affect those immune functions which are at least partially dependent on or controlled by I-region-coded molecules.

Two predictions can be made and tested concerning the role of Ia determinants in cytolytic systems and the role, if any, of I-region- specific CTL in regulating the immune response: (a) that if as we and others have shown, certain Ia specificities can serve as a third series of major histocompatibility antigens, then Ia antigens should be susceptible to the same types of antigenic modifications as H-2K- or H-2D-coded structures and thus serve as targets for CTL directed against modified-self in selected systems; and (b) that allogeneically induced I-region-specific CTL should demonstrate cross-reactivity with targets bearing modified syngeneic I-region-coded determinants. Data will be present which demonstrates that trinitrophenyl (TNP)-modified syngeneic I-region determinants can serve as targets for CTL induced by allogeneic Ia antigens.
Characterization of an amyloid fibril protein from senile cardiac amyloid.
Authors: Westermark P , Natvig J B , Johansson B
Published: June 2004

A protein, ASCA, is isolated from amyloid fibrils extracted from heart tissue of five different patients with senile cardiac amyloidosis (SCA). The proteins of all five patients showed immunological identity when reacted with an antiserum raised against one of the proteins. In contrast, no reaction was obtained with antisera against a variety of other amyloid proteins. The antiserum against the subunit protein of senile cardiac amyloid did not react with any other amyloid preparations tested, nor with extracts of normal heart tissue. Thus, the subunit protein appeared to be unique to senile heart amyloid. The protein could form fibrils in vitro, had a mol wt of about 6,000 daltons and the amino acid compositions investigated in two cases showed extensive similarities but were clearly different from that of protein AA of secondary amyloid fibrils.
Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells
Authors: Braciale TJ
Published: June 2004

Two distinct subpopulations of cytotoxic T cells are generated in the primary or secondary response of mice to type A influenza viruses. One subpopulation is specific for the immunizing virus strain. The other subpopulation shows a high degree of cross-reactivity for heterologous type A virus of a different subtype. This report examines the possibility that distinct influenza virus antigens, expressed on the surface of the infected cell, are recognized by the different subpopulations of influenza-specific cytotoxic T cells. Data are presented which demonstrate that influenza A matrix protein, an internal virion antigen, is detectable on the surface of target cells infected with influenza A viruses of different subtypes. Since this viral antigen is type specific, i.e., serologically cross-reactive among all type A influenza viruses, it could serve as the target for cross-reactive cytotoxic T cells. To further examine the specificity of the two cytotoxic T-cell subpopulations, experiments were carried out by using the inhibitor of glycoprotein synthesis - 2-Deoxy-D-Glucose 2-DG. These experiments examine first the effect of 2-DG on the expression of influenza matrix protein and viral glycoprotein on the infected cell surface and second, the susceptibility of 2-DG-treated target cells to lysis by cytotoxic T cells. 2-DG inhibits the expression of the viral hemagglutinin glycoprotein on the cell surface but does not inhibit the expression of the nonglycosylated matrix protein. Furthermore, inhibition of glycoprotein synthesis in infected target cells abrogates the reactivity of infected target cells to lysis by virus strain-specific but not cross- reactive cytotoxic T cells. These findings suggest that the influenza glycoproteins (hemagglutinin and/or neuraminidase) and the nonglycosylated matrix protein are the targets for the virus strain- specific and cross-reactive cytotoxic T cells, respectively. These results are discussed in the light of available information on influenza virus structure and the biology of influenza infection and in terms of current models for cytotoxic T-cell recognition of virus-infected cells.
Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses.
Authors: Biddison W E , Doherty P C , Webster R G
Published: June 2004

Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.
Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required.
Authors: Bick P H , Möller G
Published: June 2004

We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells.
Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation
Authors: Blanden RV , McKenzie IFC , Kees U , Melvold RW , Kohn HI
Published: June 2004

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D') bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets.

These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D') was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.
Plasmin inhibitor interactions. The effectiveness of alpha2-plasmin inhibitor in the presence of alpha2-macroglobulin.
Authors: Harpel P C
Published: June 2004

alpha2-Plasmin inhibitor and alpha2-macroglobulin were allowed to compete for the protease plasmin. The binding of the enzyme to these inhibitors was assessed by two different but comparable methods. The interactions were completed in 10 s of incubation, and transfer of plasmin from one inhibitor to the other did not occur. Almost as much plasmin was bound to alpha2-plasmin inhibitor in mixtures containing a large molar excess of alpha2-macroglobulin relative to plasmin or alpha2-plasmin inhibitor, as was bound in mixtures not containing alpha2-macroblobulin. These studies demonstrate directly the effectiveness of alpha2-plasmin inhibitor in binding and inhibiting plasmin in the presence of alpha2-macroglobulin, and suggest that the alpha2-plasmin inhibitor may be the major circulating plasmin inhibitor.
Resistance genes to murine leukemia in the I immune response gene region of the H-2 complex.
Authors: Lonai P , Haran-Ghera N
Published: June 2004

A resistance locus to leukemogenesis in mice by A-RadLV (a variant of the radiation leukemia virus) is described. This locus, Rrv-1, was mapped to subregions I-A, I-B, and I-J of the H-2 complex. It is suggested that Rrv-1 may be in complementation with a second locus to the right of it, between Rrv-1 and H-2D. This localization and the complementation of the two loci for resistance are characteristics similar to Ir genes, and indicate a possible relationship between the genetic regulation of immune responsiveness and susceptibility to leukemia.
Expression of phosphorylcholine-specific B cells during murine development
Authors: Sigal NH , Pickard AR , Metcalf ES , Gearhart PJ , Klinman NR
Published: June 2004

The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen.

These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated.
Hemagglutination by purified type I Escherichia coli pili.
Authors: Salit I E , Gotschlich E C
Published: June 2004

Many enterobacteria can cause agglutination of erythrocytes, but previous investigations have not proven which components of the bacteria are responsible. We used a strain of Escherichia coli K12 which causes mannose-sensitive hemagglutination (HA) of guinea pig cells. Common pili were purified from these bacteria by shearing them from the bacteria followed by selective precipitation in acid and ammonium sulfate. Isopycnic centrifugation in cesium chloride removed the remaining outer membrane protein contaminants. These pili are pure by electron microscopy and gel electrophoresis. By amino acid analysis, they have a mol wt of 17,099 and consist of 45% nonpolar residues. These purified pili agglutinate guinea pig erythrocytes, a reaction that is inhibited by anti-pili antibodies and by saccharides related in structure to D-mannose. Proteolytic treatment of erythrocytes does not diminish HA but rather increases the pili-induced HA of human cells. Neuraminidase enhances HA and mannosidase slightly diminishes it. It is concluded that purified pili alone cause HA of erythrocytes by binding to mannose-like molecules on the erythrocyte surface. Thus HA by bacterial pili serves as a useful model system for the mechanism of bacterial pili attachment ot cell membranes.
Immunochemical evidence for three Ia loci in the I-region of the H-2 complex.
Authors: Delovitch T L , Murphy D B , McDevitt H O
Published: June 2004

Sequential immunoprecipitation analyses of Ia antigens were performed with 125I-labeled B10, B10.A(3R), and B10.A(5R) spleen cell lysates. The results suggest the presence of one I-region associated (Ia) locus (Ia-1) in the I-A subregion. In addition, they indicate that two Ia loci map between the I-J and S regions. One locus, Ia-5, maps in the I-E subregion. The second locus, most likely Ia-3, maps in either the I-E or I-C subregion. Taken together, the data demonstrate that at least three Ia loci in the I-region of the H-2 complex code for molecules detectable by immunoprecipitation.
B-cell activation by lipopolysaccharide. Distinct pathways for induction of mitosis and antibody production.
Authors: Hoffmann M K , Galanos C , Koenig S , Oettgen H F
Published: June 2004

The role played by macrophages in two effects of lipopolysaccharide (LPS) on the immune system of the mouse-substitution for helper T cells and induction of B-cell mitosis-has been investigated. C3H/HeJ mice are unresponsive and do not produce (as other strains do) antibody to 2,4,6-trinitrophenol (TNP) conjugated with autologous mouse erythrocytes (MRBC-TNP) in the presence of LPS. We found that C3H/HeJ spleen cells produce antibody to MRBC-TNP when (a) LPS and macrophages from LPS-responsive C3HeB/FeJ mice or (b) tumor necrosis serum ([TNS] induced by LPS in responsive mice) are added. The mitotic response was not restored. The findings suggest that adjuvanticity and mitogenicity represent distinct pathways of B-cell activation by LPS, subject to different regulatory mechanisms.
Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors.
Authors: Granelli-Piperno A , Vassalli J D , Reich E
Published: June 2004

Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo.
Membrane receptors of mouse leukocytes. II. Sequential expression of membrane receptors and phagocytic capacity during leukocyte differentiation
Authors: Rabellino EM , Ross GD , Trang HTK , Williams N , Metcalf D
Published: June 2004

Analysis of four mature cell markers on mouse bone marrow leukocytes grown in vitro, demonstrated a distinct sequence of marker appearance during the terminal phases of granulocytic cell differentiation. A similar pattern of marker expression was also suggested by analysis of mature neutrophils and macrophages isolated from normal tissues. Among cultured neutrophils, receptors for the Fc portion of IgG (FcR) were first expressed on myelocytes and metamyelocytes, and then subsequently on more mature cells. Morphologically mature colony neutrophils (polymorphs) from agar cultures contained only FcR and complement receptor type two (CR(2)) (C3d receptor), and lacked both complement receptor type one (CR(1)) (C3b receptor) and the capacity to ingest latex, bacteria, or iron particles. Neutrophils from 2 and 3 wk liquid media cultures of marrow cells differed from agar grown neutrophils in that they had phagocytic capacity (particle ingestion) [Pi] in addition to FcR and CR(2). Furthermore, in the 4th and 5th wk of these continuous liquid cultures, CR(1) was also expressed, completing the surface marker profile of normal blood neutrophils. Based on these studies, the following order of appearance of these four markers on cells from the myelocytic series was proposed: FcR {arrow} FcR CR(2) {arrow} FcR CR(2) Pi {arrow} FcR CR(2) Pi CR(1).

Differential studies of tissue leukocytes containing these same markers revealed that a heterogeneity existed among morphologically mature neutrophils. Even though 95 percent of blood polymorphs contained all four markers, the same was true of only half of spleen polymorphs and only 20 percent of bone marrow polymorphs. Cells of the monocyte-macrophage series were studies in parallel with neutrophils. Cultured marrow monocytes acquired the four mature cell markers so rapidly that the order of receptor appearance could not be determined. However, it was found that CR2 was lost during the terminal phase of monocyte maturation into activated macrophages.