bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA restriction of human cytotoxic T lymphocytes specific for influenza virus. Poor recognition of virus associated with HLA A2.
Authors: McMichael A
Published: June 2004

Cytotoxic T lymphocytes (CTL), specific for influenza A/X31 virus, were generated from human peripheral blood lymphocytes. These CTL lysed target cells that were infected with the same virus and that shared HLA A or B locus antigens. Minimal lysis was observed when HLA-D antigens were shared. Not all HLA A and B antigens were equally effective. Efficient lysis of target cells was seen when HLA A1, A3, B7, B8, B27 and BW21 were shared with the CTL, but when HLA A2 was the only shared antigen lysis was usually minimal. This deficiency in CTL function associated with HLA A2 was not absolute. It is suggested that the function of this antigen might be influenced by other surface molecules on the cell and in particular the other HLA products.
Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses.
Authors: Simpson E , Mobraaten L , Chandler P , Hetherington C , Hurme M , Brunner C , Bailey D
Published: June 2004

Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function.
Immune suppression in vivo with antigen-modified syngeneic cells. I. T-cell-mediated suppression to the terpolymer poly-(Glu, Lys, Phe)n.
Authors: Cheung N K , Scherr D H , Heghinian K M , Benacerraf B , Dorf M E
Published: June 2004

The palmitoyl derivative of the linear polypeptide of poly-(L-Glu-L-Lys-L-Phe)n (GLphi) can be coupled to spleen cells directly. The intravenous administration of 2 X 10(5)--3 X 10(7) GLphi-coupled syngeneic spleen cells induces GL-phi-specific suppressor T cells in C57BL/6 nonresponder mice. The suppression is antigen specific and can be detected by the inhibition of the primary GLphi plaque-forming cell response to challenge with GLphi-fowl gamma globulin. The number of inducer cells required for suppression carry less than 0.1 microgram of antigen. Spleen cells from tolerized mice can transfer suppression to normal syngeneic recipients. The suppression is cyclophosphamide sensitive and the suppressor cells bear the Thy 1.2 marker. This method of inducing antigen-specific suppressor cells may be generally applicable to other antigen systems.
Immunological dissection of human Ia molecules.
Authors: Tosi R , Tanigaki N , Centis D , Ferrara G B , Pressman D
Published: June 2004

The immunochemical analysis of Daudi Ia molecules by a variety of alloantisera led to the recognition of at least three molecular species carrying different antigenic determinants: DRw6, DC-1, and DC-2. Genetic as well as structural evidence indicates that DRw6 and DC-1 molecules are controlled by separate, HLA-linked loci, rather than by alleles at the same locus. The alloantigenic determinants appear to be expressed on the small Ia subunit. DC-1 and DC-2 determinants discussed had not been defined by serological analysis at the population level, but were demonstrated to be present by immunochemical analysis at the molecular level.
Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow.
Authors: Korngold R , Sprent J
Published: June 2004

In two situations, transfer of normal unsensitized bone marrow cells into heavily irradiated H-2-identical allogeneic mice caused a high incidence of lethal chronic graft-versus-host disease (GVHD), i.e. mortality occuring between days of 20 and 80 postirradiation. Minor histocompatibility determinants appeared to be the main target for eliciting GVHD. Removing mature T cells from the marrow with anti-Thy 1.2 serum and complement before injection prevented GVHD. On the basis of adding purified T cells to T-cell-depleted marrow cells, it was concluded that contamination of the marrow with as few as 0.3% T cells was sufficient to cause a high incidence of lethal GVHD in certain situations. No GVHD was found with the injection of non-T cells (Thy 1.2-negative cells) or with tolerant T cells. Irradiated recipients of T-cell-depleted marrow cells remained in good health for prolonged periods. These mice showed extensive chimerism with respect to the donor marrow, normal numbers of T and B cells and were immunocompetent. The data provide no support for the view that chronic GVHD developing after bone marrow transplantation in man is the result of an attack by the progeny of the donor stem cells. The results imply that mature T cells contaminating marrow inocula are probably the main cause of GVHD seen in the clinical situation.
The type-specific polysaccharides of Streptococcus suis.
Authors: Elliott S D , Tai J Y
Published: June 2004

Streptococcus suis types 1 and 2 were subjected to digestion with lysozyme. Serologically type-specific capsular polysaccharides were isolated from the lysates by ethanol precipitation followed by Sepharose 6B chromatography. The purified type 1 polysaccharide has a Kd value of 0.074 on a Sepharose 4B column and contains galactose, glucose, N-acetyl glucosamine, N-acetyl galactosamine, and sialic acid in a molar ratio of 2.42:1.00:1.00:1.13:1.39. The type 2 polysaccharide has a Kd value of 0.185 and is composed of rhamnose, galactose, glucose, N-acetyl glucosamine, and sialic acid in a molar ratio of 1.07:3.17:1.00:0.94:1.00. A comparison is drawn between the type polysaccharides of S. suis and those of group B streptococci.
Specific adsorption of H-2-restricted cytotoxi T cells to macrophage monolayers.
Authors: Kees U , Müllbacher A , Blanden R V
Published: June 2004

These experiments tested whether Tc cells specific for foreign antigen (X) plus self H-2 adsorbed to macrophage monolayers displaying (a) X with allogeneic H-2; (B) self H-2 alone; (c) X plus self H-2. Specific adsorption occurred only in case (c), a result compatible with altered self and requiring further operational assumptions in dual recognition models.
Myelin basic protein serum factor. An endogenous neuroantigen influencing development of experimental allergic encephalomyelitis in Lewis rats.
Authors: Fujinami R S , Paterson P Y , Day E D , Varitek V A
Published: June 2004

Age-related concentrations of myelin basic protein serum factor (MBP-SF), an endogenous neuroantigen detected and quantitated by inhibition of binding of rat myelin basic protein (RMBP) antibody with 125I-RMBP reagent antigen and immunochemically indistinguishable from native RMBP in this respect, reach peak levels as high as 21 ng/microliter among 2-3-wk-old normal suckling Lewis rats. Levels then progressively decline to low, usually undetectable levels of less than or equal to 0.6 ng/microliter MBP-equivalents in adult animals by 7 wk of age. MBP-SF levels are inversely related to the age-related increasing capacity of maturing Lewis rats to develop experimental allergic encephalomyelitis (EAE) after sensitization to MBP of syngeneic, but not xenogeneic, origin. MBP-SF appears to be an endogenous neuroimmunoregulatory product of potential importance for immunologic tolerance to autologous RMBP in Lewis rats.
Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro.
Authors: Steinman R M , Kaplan G , Witmer M D , Cohn Z A
Published: June 2004

Dendritic cells (DCs; 1) have been purified from mouse spleen in good yield. Spleen cell suspensions were floated on dense bovine plasma albumin (BPA) columns, and the low density fraction was adhered to glass (2). The adherent cells consisted of DCs and immature macrophages most of which eluted in a viable state from the culture dish after overnight incubation. The macrophages were then removed by selective rosetting with opsonized erythrocytes and recentrifugation on dense BPA. This protocol resulted in a purified DC fraction, containing 1--3 X 10(5) DCs/spleen, which was homogeneous and distinctive in its properties. All cells exhibited the phase contrast and transmission electron microscopy (EM) cytologic features that were previously described for freshly isolated adherent DCs. By scanning EM, most purified DCs exhibited a remarkable array of bulbous protrusions of varying length and shape, unlike any other lymphoid cell. All DCs expressed surface Ia and other major histocompatibility complex (MHC)-linked alloantigens. DCs, however, lacked surface Ig and T-cell antigens, and did not bind or interiorize opsonized erythrocytes. Purified DCs have been maintined in vitro for 3 days. Recovery of cultured purified cells was 70% or more of starting cell numbers. When [3H]uridine-tagged DCs were mixed with nonlabeled heterogeneous spleen cells, 70--80% of the labeled DCs were recovered as viable cells 2--3 days later. Purified DCs did not readhere to tissue culture surfaces and did not proliferate, even when cultured with mitogenic doses of concanavalin A and lipopolysaccharide. Finally, DCs did not change their cytologic or surface properties after 3 days of culture. These observations extend the evidence that DCs are a novel cell type and provide useful properties and techniques for their further study.
Regulatory mechanisms in cell-mediated immune responses. VII. Presence of I-C subregion determinants on mixed leukocyte reaction suppressor factor.
Authors: Rich S S , David C S , Rich R R
Published: June 2004

The presence of H-2 gene products on mixed leukocyte reaction (MLR) supressor factor was investigated by passage of MLR-suppressor factor (SF) over solid immunoadsorbents prepared with various anti-H-2 subregion sera. Antisera with specificity for all or certain I subregion determinants removed or significantly reduced suppressor activity; adsorption was not consistent with K or D region specificity. The single I subregion specificity common to all adsorbing preparations was I-C. Serologic differentiation of I-C products of k and d haplotypes expressed on MLR-SF was established with antisera prepared in I-Cd/I-Ck disparate strain combinations. These sera define allelic T cell restricted Lad determinants encoded by I-C genes. MLR-SF prepared from (BALB/c X CBA)F1 mice and exposed to the I-Cd and I-Ck specific adsorbents demonstrated d and k haplotype specific adsorption respectively. F1 suppressor activity adsorbed on an anti-I-Cd column was eluted by glycine-HCl buffer and suppressed only BALB/c (H-2d) responses. B10.A suppressor activity was removed by anti-I-Cd sera, but was unaffected by anti-I-Ck sera, indicating that B10.A suppressor activity is encoded by an I-C subregion derived from the d haplotype. Antisera with anti-I-Jk specificity did not remove suppressor activity of various H-2k factors. Finally, adsorption with antisera directed against H-2-associated determinants of the allogeneic cell used to stimulate suppressor factor generation demonstrated that sensitizing alloantigens are not components of MLR suppressor factor. Thus among the major histocompatibility complex (MHC)-controlled suppressor factors, MLR suppressor factor is uniquely determined by the I-C subregion.
Human macromolecular insoluble cold globulin (MICG). I. T-cell origin of T-MICG and null cell origin of N-MICG.
Authors: Hauptman S P , Kansu E , Serno M , Godfrey S
Published: June 2004

Although surface immunoglobulin characterizes B cells in man, there are few surface markers that distinguish T cells. We have described a new protein synthesized in human T cells, termed T-MICG. This protein is a macromolecule of 225,000 daltons, is insoluble in the cold, and migrates as a beta-globulin on electrophoresis. Separation of human peripheral blood lymphocytes into T and B-cell populations by rosette sedimentation and anti-human-Fab columns clearly demonstrated the T-cell origin of the 225,000 dalton component. Furthermore, null cells were shown to synthesize a protein of 185,000 daltons, termed N-MICG, with physical properties similar to T-MICG, T-MICG and N-MICG were shown to be antigenically dissimilar, employing antiserum to each of these proteins. The present studies demonstrate two novel cell surface markers, T-MICG and N-MICG, which characterize T cells and null cells, respectively.
G(AKSL2): a new cell surface antigen of the mouse related to the dualtropic mink cell focus-inducing class of murine leukemia virus detected by naturally occurring antibody.
Authors: Stockert E , DeLeo A B , O'Donnell P V , Obata Y , Old L J
Published: June 2004

Normal mouse sera were tested for cytotoxic antibody to surface antigens of cultured monolayer cells infected with AKR-derived ecotropic MuLV, xentropic MuLV, or dualtropic MCF 247 MuLV. Antibody to ecotropic MuLV-infected cells was found in a proportion of C57BL/6, C3Hf/Bi, AKR-Fv-1b, and (C3Hf/Bi X AKR)F1 mice, but not AKR or (AKR X C3Hf/Bi)F1 mice. Antibody to xenotropic MuLV-infected cells was virtually restricted to C57BL/6 mice. Antibody to MCF 247-infected cells was found in all strains tested, including AKR mice. Absorption analysis of (C3Hf/Bi x akr)f1 and AKR-Fv-1b sera with selective reactivity for MCF 247-infected cells showed that these sera recognize distinctive antigens on MCF 247-infected cells that are not present on ecotropic or xenotropic MuLV-infected cells. The transplantable AKR spontaneous leukemia AKSL2 was found to be uniquely sensitive to the cytotoxic action of naturally occurring antibody to MCF 247-related antigens and absorption tests with AKSL2 as the target cell and sera from a single AKR-Fv-1b mouse have permitted the definition of a new MuLV-related cell surface antigen, which has been designated G(AKSL2). Thymocytes from young mice of high leukemia-incidence strains (AKR, C58, and PL) express G(AKSL2), whereas thymocytes from 12 other strains do not. In AKR mice, the antigen is expressed in higher amounts on cells from thymus and bone marrow than on spleen cells. All AKR spontaneous leukemias tested express G(AKSL2), as did three MuLV-induced leukemias arising in G(AKSL2)- strains. Five X-ray-induced leukemias of G(AKSL2)- strains were G(AKSL2)-, as were MuLV+ and MuLV- chemically induced sarcomas. In the limited survey conducted to date, natural antibody to G(AKSL2) has been restricted to strains expressing G(AKSL2) in their normal tissues: AKR, AKR congenic mice AKR-Fv-1b and AKR hybrid mice (C3Hf/Bi x akr)f1 and (C57BL/6 X AKR)F1. In vitro G(AKSL2) induction tests involving MuLV infection of cultured monolayer cells showed that 8 of 12 newly isolated dualtropic MuLV shared the property of G(AKSL2) induction with the prototype MCF MuLV, MCF 247. Of the 12 ecotropic MuLV tested, only the N-tropic MuLV isolated from a leukemia originally induced by Passage A Gross virus induced G(AKSL2). The xenotropic and amphotropic MuLV isolates tested lacked G(AKSL2) inducing activity. Recognition of the g(aksl2) system provides a way to trace the origin and natural history of a class of dualtropic MCF MuLV in the mouse and to determine whether natural antibody to G(AKSL2) plays a role in AKR leukemogenesis.
Immunological studies of T-cell receptors. II. Limited polymorphism of idiotypic determinants on T-cell receptors specific for major histocompatibility complex alloantigens.
Authors: Bellgrau D , Wilson D B
Published: June 2004

These studies explore the extent of genetic polymorphism in the expression of anti-MHC receptors by T cells in different strains of rats. This question was approached with the use of the model of specifically induced GVH resistance in F1 rats which has been shown to reflect a specific T-cell mediated immune response against parental strain T cell anti-MHC receptors specific for host alloantigens. When A/B F1 rats derived from MHC incompatibile matings are immunized with lymphocytes from one parental strain (A they display a specific resistance to anti-B GVH reactivity caused by T cells from that parental strain, but not anti-AGVH reactions from the other. In addition, they resist anti-B GHV reactivity by T cells from third-party donors (C, D, E,...), a finding taken to indicate that the idiotypes of anti-MHC receptors on T cells, recognized by other T cells, show little or no polymorphism. This conclusion suggests that anti-MHC receptors are shared in the species and may be encoded, at least partially, by germ-line genes.
Wild mouse RNA tumor viruses. A nongenetically transmitted virus group closely related to exogenous leukemia viruses of laboratory mouse strains.
Authors: Barbacid M , Robbins K C , Aaronson S A
Published: June 2004

Type-C RNA viruses isolated from wild mice are causative of naturally occurring neoplasia and neurologic diseases. Biochemical and immunologic characterization of this virus group revealed that amphotropic viruses isolated from wild mice trapped in separate geographical areas are indistinguishable, whereas amphotropic and ecotropic viruses naturally infecting the same animal are env gene variants. Molecular hybridization studies established that neither host range variant is endogenous to the Mus musculus genome, although each demonstrates partial nucleotide sequence homology. Wild mouse type-C viruses exhibited much closer molecular and antigenic relatedness to the exogenous virus subgroup (Friend-, Moloney-, and Rauscher-MuLV) than to prototype endogenous viruses isolated from laboratory mouse strains. The evidence indicates that exogenous mouse type-C viruses have been maintained in nature over a long period of evolution as a separate virus group, causative of tumors in mice by a mechanism solely involving their transmission as infectious agents.
Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten.
Authors: Kaplan R B , Quintáns J
Published: June 2004

F1 male mice with the CBA/N X-linked defect that are unable to produce plaque-forming cell responses to phosphorylcholine (PC) provide normal PC-specific helper T-cell activity when compared to F1 female littermates. Inhibition of helper activity with anti-idiotypic antiserum indicates that PC-specific T cells from both NBF1 female and male mice possess predominantly BALB/c myeloma protein HOPC-8 idiotypic determinants. Therefore, the CBA/N defect cannot be explained as a deletion of genes coding for V-region anti-PC specificities. The demonstration of helper activity in NBF1 male mice, which occurs in the absence of anti-PC antibody synthesis, also demonstrates the endogenous origin of the T-cell receptor.
Prostaglandins are necessary for osteoclast-activating factor production by activated peripheral blood leukocytes.
Authors: Yoneda T , Mundy G R
Published: June 2004

The production of osteoclast-activating factor (OAF) by normal human peripheral blood leukocytes stimulated by phytohemagglutinin was inhibited by a series of structurally unrelated inhibitors of prostaglandin synthetase. Inhibition of OAF production by these agents was reversed by adding prostaglandins of the E series back to the leukocyte suspension. These results indicate that prostaglandin synthesis is necessary for OAF production.
Gene complementation in the T-lymphocyte proliferative response to poly (Glu55Lys36Phe9)n. A demonstration that both immune response gene products must be expressed in the same antigen-presenting cell.
Authors: Schwartz R H , Yano A , Stimpfling J H , Paul W E
Published: June 2004

The immune response (Ir) to the random copolymer GLphi depends upon the function of two Ir genes, Ir-GLphi-beta[beta] and Ir-GLphi-alpha[alpha], mapped to the I-A and I-E/C subregions of the major histocompatibility complex, respectively. In this paper, the site(s) of expression of the products of these two Ir genes was examined by evaluating T-lymphocyte proliferative responses of bone marrow radiation chimeras. Chimeras were created in [alpha+beta- X alpha-beta+]F1 responder mice by lethal irradiation and reconstitution with a mixture of bone marrow cells from both parental strains. These chimeras failed to respond to GLphi, although they were capable or responding to the much weaker antigens, (T,G)-A--L, TEPC-15, pigeon cytochrome c, and (H,G)-A--L. This failure to respond to GLphi was shown not to be the result of a cryptic mixed lymphocyte reaction, as similar chimeras created in (alpha+beta+ X alpha-beta+)F1 mice responded well to GLphi, although they possessed almost the same potential histoincompatibility. Furthermore, the lack of response to GLphi could not be attributed to a general failure of the two parental cell types in the chimeras to collaboratc with each other, as each chimeric parental cell type could respond to dinitrophenyl conjugated ovalbumin presented on nonimmune spleen cells from the other parent. Thus, the failure of low responder parental into F1 high responder chimeras to generate an immune response to GLphi suggests that immune competence for this antigen requires at least one cell type in the immune system to express gene products of both the Ir-glphi-alpha and -beta genes, i.e. one cell must be of high responder genotype. The the antigen-presenting cell is one such cell type was shown by experiments in which GLphi-primed T lymphocytes from responder F1 mice were stimulated with antigen bound to nonimmune spleen cells. Only spleen cells from responder F1 and recombinant mice could present GLphi. Neither of the two complementing nonresponder parental spleen cell populations, either alone or mixed together, could present GLphi, although both could present purified protein derivative of tuberculin. This was shown to be the case for T cells positively selected in vitro as well as freshly explanted T cells. Thus, both Ir-GLphi-alpha and Ir-GLphi-beta gene products must be expressed in the same antigen-presenting cell to generate a T-lymphocyte proliferative response to GLphi. The implications of these findings for models of two gene complementation are discussed.
Differential response of early erythropoietic and granulopoietic progenitors to dexamethasone and cortisone.
Authors: Zalman F , Maloney M A , Patt H M
Published: June 2004

The sensitivity of erythropoietic (BFU-E) and granulopoietic (CFU-C) progenitor cells to dexamethasone and cortisone was studied in cultures of mouse bone marrow. Although the log dose-response relationships had a similar form, the BFU-E were much more sensitive than the CFU-C to either glucocorticoid. The dexamethasone concentration for 50% inhibition was 3 X 10)-9) M for BFU-E and 60 X 10(-9) M for CFU-C. The differential sensitivity to cortisone was even greater, with 60% inhibition of BFU-E and 18% inhibition of CFU-C at 0.1 microgram/ml. These findings suggest a specific rather than a general response to glucocorticoids and indicate that granulocyte-macrophage progenitors are less affected than early erythroid progenitors by physiologic concentrations of these hormones.
Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide.
Authors: Nathan C F , Brukner L H , Silverstein S C , Cohn Z A
Published: June 2004

Lymphoma cells were rapidly lysed by activated macrophages and granulocytes in the presence of PMA. Release of 51Cr from lymphoma cells correlated closely with their destruction as viewed by scanning electron microscopy, and with reduction in the number of trypan blue-excluding cells. The standard assay involved 51 Cr release measured at 4.5 h, but injury appeared to be complete in 1 h. Of eight different types of effector cells tested, only those releasing abundant H2O2 in response to PMA were effective, that, is BCG-, C. parvum-, or casein-activated macrophages, or thioglycollate-elicited granulocytes. Normal macrophages, J774 cells, or macrophages elicited with thioglycollate broth or proteose-peptone were ineffective. BCG-activated macrophages and granulocytes caused 50% specific release of 51Cr from P388 lymphoma cells at E:T ratios between 1.4 and 4.5, and from mouse erythrocytes at E:T ratios of 0.017 to 0.025. 10 types of target cells varied widely in their susceptibility to lysis by reagent H2O2, with one-half maximal lysis occurring at H2O2 concentrations ranging from 3.63 X 10(-6) M to 3.85 X 10(-5) M. Effector cells were expected to generate approximately that much H2O2 during the period of injury. Susceptibility of the target cells to lysis by PMA-triggered granulocytes correlated closely with their sensitivity to H2O2 (r = 0.98). The membrane-active agents LPS and digitonin, which did not trigger H2O2 release, did not trigger cytotoxicity. The dose-response curve for triggering of H2O2 release by PMA was identical to that for triggering cytotoxicity. These results provided strong circumstantial evidence for the importance of H2O2 in extracellular cytolysis by activated macrophages and granulocytes when pharmacologically triggered.
Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.
Authors: Eckner R J , Hettrick K L
Published: June 2004

A latent form of persistent infection can be established in susceptible adult mice inoculated with a preparation of defective Friend spleen focus-forming virus (SFFV) purified free from standard leukemia-inducing helper virus (LLV-F). SFFV persistence was initially observed using an in vivo rescue technique in which SFFV could be directly rescued to form splenic foci of malignant erythropoiesis in mice. At approximately 30 d after virus inoculation however, SFFV could not be rescued after inoculation of LLV-F indicating that persistently infected (i.e., SFFV+) mice were either immume to exogenous helper virus or able to express SFFV-associated defective-interfering (DI) function(s). Persistent infection by SFFV was further documented using an in vitro rescue technique and ultimately resulted in the induction by SFFV of erythroleukemia in the absence of polycythemia or overt virus production. However, SFFV rescued by LLV-F from persistently infected normal and transformed hemopoietic cells was able to induce polycythemia in adult mice suggesting that this is a helper controlled property of the Friend virus complex. Transplantable SFFV-induced erythroleukemic cells could be retrieved from persistently infected yet histologically normal mice. The duration of SFFV persistence in normal spleen tissue suggests that the SFFV provirus resides in either a long-lived or pluripotent hemopoietic cell. Further, certain changes occurred, presumably in the membranes of persistently infected cells, which preceded the overt development of Friend leukemia and facilitated the definition of an SFFV preleukemic phase. Cell surface alterations were revealed using cell transfer techniques. Hemopoietic cells harboring a rescuable SFFV failed to proliferate when inoculated into lethally irradiated, syngeneic adult mice. In contrast, the transformed progeny of preleukemic cell populations and spleen cells transformed by FV complex (i.e., cells replicating both SFFV and LLV-F) were not rejected. This result suggests that histologically normal SFFV+ preleukemic cells express an antigen recognition site which is not present on overtly transformed cells and which may be a pertinent surveillance target for host anti-leukemogenic reactions.
Naturally occurring lymphocyte-mediated immunity to endogenous type-C virus in the mouse. Blocking of the lymphocyte reactivity with antisera to the virus.
Authors: Kende M , Hill R , Dinowitz M , Stephenson J R , Kelloff G J
Published: June 2004

The natural immune response in mice to their endogenous type-C viruses involves a complex interaction between cellular and humoral immune mechanisms. The virus-specific immune reactivities are a function of age and appear only subsequent to endogenous virus expression. Cellular immune activity was found to reside in a population of lymphocytes that were characterized as natural killer cells based on their absence of theta surface antigens or immunoglobulin or complement receptors. Cellular and humoral virus-specific immune responses co-occur in the same animal and pretreatment of virus-positive target cells with sera from virus-positive aging mice is capable of partially blocking the cytotoxic activity of reactive lymphocytes. The blocking activity of sera from individual mice increases as a function of age and endogenous virus expression and is highly correlated with the virus-specific complement-dependent cytotoxic activity of these sera. Mouse sera, whether naturally immune or immune as a result of hyperimmunization with type-C virus, exhibit blocking activity that can be removed by absorption with purified type-C virus or purified viral glycoprotein (gp 70) but not by absorption with noninfected syngeneic cells. High-titered and highly specific antisera directed against certain individual R-MuLV structural proteins reveal blocking activity. Monospecific antisera to gp 70 and p 12 exhibited high-titered blocking reactivities which are absorbable by the respective purified proteins. Blocking activity of antisera directed against other viral structural proteins could not be excluded with certainty. These findings raise the possibility that immunity in the mouse to endogenous type-C virus or virus-infected cells involves competition between serum-blocking activity and natural-killer cell activity and further provides a unique model system for studying the mechanism of action of blocking antisera known to have monospecific reactivity against defined and purifiable transplantation antigens.
Immunological properties of conjugates of ragweed pollen antigen E with methoxypolyethylene glycol or a copolymer of D-glutamic acid and D-lysine.
Authors: King T P , Kochoumian L , Chiorazzi N
Published: June 2004

The major allergen of ragweed pollen, antigen E, was modified by coupling its amino acid groups with either methanol, methoxypolyethylene glycol (MPEG) of 5,000 daltons, or a synthetic copolymer of D-glutamic acid and D-lysine (DGL) of 34,000 daltons, all appropriately activated. The conjugates were characterized chemically and immunologically. Compared to the native antigen, the methoxy conjugate showed little reduction in allergenic activity, but the other two conjugates showed strong reductions, as measured by heterologous passive cutaneous anaphylaxis in rats sensitized with murine anti-antigen E reaginic sera. The MPEG conjugate was apparently nonimmunogenic in mice known to be high responders to the native antigen. MPEG and DGL conjugates retained the immunosuppressive property of the native antigen as subcutaneous treatment of antigen E sensitized mice with these two conjugates led to significant long-lasting depression of their antigen E-specific IgE and IgG antibody levels. These immunological changes are believed to result from reduction of antigenic valency and specificity upon coupling the bulky molecules to the protein antigens.
Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type.
Authors: Blanden R V , Andrew M E
Published: June 2004

Chimeras produced by reconstitution of 950 rads irradiated type A or type B host mice with (AXB)F1 fetal liver stem cells were examined in primary (in vivo) and secondary (in vitro) Tc-cell responses to ectromelia virus infection. Of 33 individual chimeras which gave primary responses, 26 produced significant specific lysis of infected targets of both A and B type, though host type targets were invariably lysed more efficiently (host bias). The other 7 chimeras gave lysis of infected host type targets only (absolute restriction). 12 individual chimeras were used in secondary responses. Nine showed host bias, and three showed absolute restriction. Whether an individual chimera showed host bias or absolute restriction seemed to be unrelated to whether the response was primary or secondary, to the time after reconstitution (ranging from 4 to 22 wk), to strain of mouse, or to the batch of fetal liver stem cells used.
Regulation of ige antibody production by serum molecules. III. Induction of suppressive activity by allogeneic lymphoid cell interactions and suppression of IgE synthesis by the allogeneic effect
Authors: Katz DH
Published: June 2004

Antibody responses of the IgE class are, like other immunoglobulin classes, regulated by a finely-tuned network of complex cellular and molecular interactions (1). Previous studies conducted in our laboratory (2, 3) have provided new insights into the differences in control mechanisms that result in individuals manifesting either the high (allergic) or low (nonallergic) IgE responder phenotype. These experiments have shown that certain manipulations (i.e. low dose X-irradiation) convert normally low responder mice to high IgE responders, apparently by diminishing a suppressor T-cell mechanism which normally dampens, rather selectively, IgE antibody production in such individuals. Similar findings have been made by Watanabe et al. (4).

Recently, we have been studying the types of manipulations that could reverse the high IgE responsive state back to a low one. These studies (2, 3, 5, 6) have demonstrated that the high IgE responses induced in low responder mice can be substantially diminished, and even abolished, by passively transfusing serum or ascetic fluid from donor mice previously inoculated with mycobacterial-containing complete Freund's adjuvant (CFA). Because the suppressive activity of CFA-immune serum or ascitic fluid is so highly selective for IgE antibody production, we have recently termed these serum substances suppressive factors of allergy (SFA) (2, 3).

The present study was undertaken to determine whether alternative means, particularly those that avoid administration of CFA, could be devised for the induction of SFA. Herein, we report the effectiveness of allogeneic lymphoid cell interactions in inducing SFA, both in vivo and in vitro, as well as the potent suppressive effects of an in vivo allogeneic effect on irradiation enhanced IgE antibody production in low responder mice.
Anti-self HLA may be clonally expressed.
Authors: Goulmy E , Hamilton J D , Bradley B A
Published: June 2004

A monolayer absorption technique was used to test the hypothesis that killer cells directed to self HLA-associated minor histocompatibility antigens (H-Y) were divisible into subsets. The results showed that sensitized killer cells, which recognized two combined antigens HLA-A2; H-Y and HLA-B7; H-Y could indeed be divided into two populations. One was directed to HLA-A2; H-Y and the other to HLA-B7; H-Y. These results can be interpreted in the context of the altered self hypothesis. However, when interpreted in the context of the dual recognition hypothesis, they strongly suggest that independant clones of killer T cells exist which are committed to the recognition of self HLA.
T-cell regulation of murine IgA synthesis.
Authors: Elson C O , Heck J A , Strober W
Published: June 2004

In studies reported here, the polyclonal activator lipopolysaccharide was used to stimulate the synthesis and secretion of IgM, IgA, and IgG in cultures of mouse lymphoid cells. The total immunoglobulin of each class which resulted was measured by specific double-antibody radioimmunoassays. The effect of Con A-activated T cells from various tissues on such immunoglobulin synthesis was then assessed. Variations in regulatory T-cell activity among the various lymphoid tissues for IgA but not for IgM or IgG was observed. In particular, Peyer's patches T cells were found to contain a high level of IgA T-cell helper activity compared to that of spleen or peripheral lymph node. The independent variation of T-cell regulatory activity for IgA as compared to that for IgM and IgG among the different tissues is most consistent with there being a separate subset of T cells specifically regulating IgA. The significance of these findings for the understanding of the secretory immune system is discussed.
Endotoxin protein is a mitogen and polyclonal activator of human B lymphocytes.
Authors: Goodman G W , Sultzer B M
Published: June 2004

Endotoxin protein (EP) has been shown to be a mitogen and polyclonal activator of human peripheral blood lymphocytes. EP stimulates proliferation of B lymphoyctes in the absence of T cells, and this activation is nonspecific by a number of parameters. Additionally, EP mitogenesis, but not polyclonal activation, is inhibited in the presence of human serum, suggesting that these events are dissociable. In these studies, EP appears to be equivalent to or better than pokeweed mitogen in stimulating nonspecific antibody production in vitro.
Quantitative differences in the expression of parentally-derived H-2 antigens in F1 hybrid mice affect T-cell responses.
Authors: O'Neill H C , Blanden R V
Published: June 2004

Quantitative absorption with specific anti-H-2 sera has shown that the H-2Kb and H-2Dd antigens coded by the B10.A(5R) haplotype are expressed in about fourfold lower amount on the spleen cells of [B10.A(5R) X B10.A(2R)]F1 hybrids than on parental B10.A(5R) cells. In contrast, the H-2Kk and H-2Db antigens of B10.A(2R) are expressed equally on parental and F1 cells. These quantitative differences are reflected in cytotoxic T-cell (Tc-cell) function. Macrophage target cells from F1 mice are killed less efficiently than B10.A(5R) targets by alloreactive or H-2 restricted Tc cells specific for H-2Kb or H-2Dd, and spleen cells of F1 mice are less efficient stimulators of alloreactive Tc cells specific for B10.A(5R) H-2 antigens, whereas F1 and B10.A(2R) cells are equal as targets and stimulators for Tc cells recognizing B10.A(2R) H-2 antigens.
Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro.
Authors: McIntyre J A , Faulk W P
Published: June 2004

This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction.
Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin.
Authors: Braciale T J
Published: June 2004

Purified type A influenza viral hemagglutinin stimulates an in vitro cell-mediated cytotoxic cell response that exhibits a high degree of specificity for the immunizing hemagglutinin. The response magnitude is proportional to the hemagglutinin dose used for stimulation. The lytic activity of the effector cells is H-2 restricted. Analysis of the specificity of the response indicated that these cytotoxic T cells readily distinguish target cells expressing serologically unrelated hemagglutinin from target cells bearing hemagglutinins serologically related to the stimulating hemagglutinin. Further analysis of the fine specificity of cytotoxic T-cell recognition with serologically cross-reactive type A influenza hemagglutinins revealed a hierarchy of cross-reactivity among these hemagglutinins that was the converse of the serologic hierarchy. These results are discussed in terms of possible differences and similarities in the specificity repertoire of cytotoxic T cells and antibodies. Possible implications of these findings from the standpoint of cytotoxic T-cell induction are also discussed.
The appearance of transition forms between monocytes and Kupffer cells in the liver of rats treated with glucan. A cytochemical and ultrastructural study.
Authors: Deimann W , Fahimi H D
Published: June 2004

A massive accumulation of mononuclear phagocytes in the rat liver was found after the injection of glucan, a beta-1,3-polyglucose. Portal vessels and central veins contained large numbers of rounded and elongated cells which were adherent to the endothelium. By scanning electron microscopy most of these cells exhibited prominent lemellopodia, raised ridge-like profiles and blebs, the typical features of mononuclear phagocytes. Peroxidase cytochemistry revealed that whereas most cells in portal vessels were monocytes with peroxidase positive and negative granules, the majority of cells in central veins were macrophages exhibiting peroxidase activity in nuclear envelope (NE) and endoplasmic reticulum (ER). In sinusoids monocytes and macrophages were seen side by side. The major finding of the present study was that some cells, adherent to the endothelium or portal vessels or to the lining of sinusoids, exhibited a peroxidase pattern intermediate between monocytes and Kupffer cells, i.e. strong peroxidase activity in cytoplasmic granules, as well as a weak to moderately positive peroxidase reaction in NE and ER. These intermediate cells also contained peroxidase-negative granules with halo, which are usually seen in monocytes. Furthermore, examination of serial ultrathin sections of typical Kupffer cells revealed numerous peroxidase-positive granules and peroxidase-negative granules with halo in their cytoplasm. Finally, dividing Kupffer cells with positive peroxidase reaction in ER were found. These in vivo observations provide ultrastructural and cytochemical evidence in support of the concept of derivation of Kupffer cells from monocytes, demonstrating in addition that Kupffer cells are capable of self-replication in situ.
A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.
Authors: Meruelo D
Published: June 2004

Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.
Metabolic similarities between fertilization and phagocytosis. Conservation of a peroxidatic mechanism.
Authors: Klebanoff S J , Foerder C A , Eddy E M , Shapiro B M
Published: June 2004

At the time of fertilization, sea urchin eggs release a peroxidase which, together with H2O2 generated by a respiratory burst, is responsible for hardening of the fertilization membrane. We demonstrate here that the ovoperoxidase of unfertilized eggs is located in cortical granules and, after fertilization, is concentrated in the fertilization membrane. Fertilization of sea urchin eggs or their parthenogenetic activation with the ionophor A23187 also results in (a) the conversion of iodide to a trichloroacetic acid-precipitable form (iodination), (b) the deiodination of eggs exogenously labeled with myeloperoxidase and H2O2, (c) the degradation of thyroxine as measured by the recovery of the released radioiodine at the origin and in the inorganic iodide spot on paper chromatography, and (d) the conversion of estradiol to an alcohol-precipitable form (estrogen binding). The iodination reaction and the binding of estradio occurs predominantly in the fertilization membrane where the ovoperoxidase is concentrated. From the estimation of the kinetics of incorporation of iodine, we determine that the peroxidative system is active for 30 min after fertilization, long after hardening of the fertilization membrane is complete. Most of the bound iodine is lost during the hatching process. Iodination of albumin is catalyzed by the material released from the egg during fertilization, when combined with H2O2 and iodide. Iodination, thyroxine degradation, and estradiol binding are inhibited by azide, cyanide, aminotriazole, methimazole, ascorbic acid and ergothioneine, all of which can inhibit peroxidase-catalyzed reactions. These responses of the sea urchin egg to fertilization are strikingly similar to the changes induced in polymorphonuclear leukocytes by phagocytosis and, in both instances, a peroxidative mechanism may be involved.