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F Y Liew

Publications and source records attributed to F Y Liew.

At least 181 records · Page 10Linked to original sources
PubMed1988

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. II. Partial biochemical characterization.

Culture supernatants of splenic T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a suppressive substance which can inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens. The suppressive substance is distinct from T. cruzi antigen inasmuch as the supernatant depleted of any residual T. cruzi antigen by an affinity column still retains the suppressive activity, whereas addition of T. cruzi antigens to control supernatant did not confer suppressive function. The suppressive supernatant does not contain detectable levels of IL-1, IL-2, IL-3, or IFN-gamma but a modest level of IL-1 and IL-2 inhibitory activities. However, both these inhibitory activities elute at a different position from the DTH suppressive activity on gel filtration. The DTH suppressive activity is heat labile (1 h, 56 degrees C), cryostable, but destroyed by trypsin treatment. It binds to ricin but not to lentil lectin. Sepharose 4B gel filtration and HPLC analysis in mild chaotropic agents (urea, ethylene glycol) demonstrate that the suppressive substance has an apparent Mr of 30 to 60 kDa, but full DTH-suppressive activity is retained only in an aggregated form.

Animals↗
PubMed1988

Susceptibility to murine cutaneous leishmaniasis correlates with the capacity to generate interleukin 3 in response to leishmania antigen in vitro.

Spleen cells from genetically susceptible BALB/c mice infected with Leishmania major produced higher levels of IL-3 in response to leishmania antigens or concanavalin-A in vitro compared to that of genetically resistant CBA mice throughout the course of infection. The capacity to generate IL-3 in BALB/c mice increased with disease progression. The correlation between susceptibility to L. major infection and the capacity of spleen cells to produce IL-3 also extends to other mouse strains. Thus genetically highly resistant CBA and Biozzi Low mice are low IL-3 producers, whereas the highly susceptible BALB/c and Biozzi High mice are high IL-3 producers. The resistant C57BL/10 and C3H mice produce intermediate levels of IL-3. BALB/c mice recovered from L. major infection following a sublethal dose of gamma-irradiation are refractory to further infection. The capacity of the spleen cells from these cured mice to produce IL-3 upon a challenge infection was similar to those of the resistant CBA mice. The IL-3 generated by activated T cells was measured by IL-3 dependent cell lines, 32D and FDC-P2. The spleen cells from infected BALB/c mice also contain a population of IL-3 responding cells whose number increases as disease progresses. A similar population of IL-3 responding cells was barely detectable in the resistant CBA mice or BALB/c mice rendered immune by prior gamma-irradiation. These results therefore demonstrate a direct correlation between the susceptibility to L. major infection and the capacity of splenic T cells from infected mice to produce a continuous elevated level of IL-3. The possible role of IL-3 in the immune regulation of cutaneous leishmaniasis is discussed.

Animals↗
PubMed1988

Immune suppressor substance in experimental chagas disease.

Specific and generalized immune suppression has been reported in several acute and chronic parasitic infections. In Chagas disease, soluble suppressor substances have been demonstrated in murine experimental models, but the nature and origin of these substances remain uncertain. Here, Eddy Liew reviews recent findings on immune suppression in inbred mouse strains infected with Trypanosoma cruzi. He suggests that production of suppressor substances may be an appropriate means to balance host-protective immunity with the possible risk of autoimmune disease, but, because of the apparent genetic restriction of suppressor substance production, raises doubts about its true biological significance.

Journal Article↗
PubMed1988

Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice.

Stable transposon-generated auxotrophic mutations in aroA, purA, and purE or aroA and purA together were introduced into Salmonella typhimurium strains which were virulent in mice. Strains harboring any of these mutations were attenuated when tested in BALB/c mice. purE strains were less attenuated than aroA or purA strains. Both aroA and purA mutants persisted for several weeks in the livers and spleens of the mice after intravenous infection, although the numbers of viable cells detected at various times after infection differed. aroA strains persisted at a higher level than purA strains and were effective live vaccines given intravenously or orally. purA strains were ineffective as oral vaccines and were poor intravenous vaccines. Strains harboring both aroA and purA mutations together were ineffective vaccines when administered orally or intravenously even though they persisted in the livers and spleens of the mice for long periods after intravenous infection.

Administration, Oral↗
PubMed1987

Prophylactic immunization against experimental leishmaniasis. VI. Comparison of protective and disease-promoting T cells.

In previous studies, we reported that mice immunized i.v. with lethally irradiated Leishmania major promastigotes developed substantial resistance to a subsequent L. major infection. However, such protection could be totally suppressed by prior s.c. injection with the same antigens. Both the protective immunity and the inhibition of its induction could be adoptively transferred with specific Lyt-2- T cells. Here, we present evidence showing that protection and disease promotion resulting from i.v. or s.c. immunization, respectively, are mediated by functionally distinct subsets of T cells. In a series of titration experiments, it was found that freshly isolated T cells derived from prophylactically i.v. immunized BALB/c mice were either protective (greater than 10(7) cells/recipient) or ineffective (less than 10(7) cells/recipient). No exacerbation of disease was observed at any dose. Conversely, T cells from mice immunized s.c. either accelerated disease development and inhibited protective immunization (greater than 10(7) cells/recipient) or had no effect (less than 10(7) cells/recipient). No protection was observed at any dose tested. In mixed transfer experiments, increasing numbers of T cells from s.c. immunized donors progressively inhibited the protective effect of T cells from i.v. immunized donors. Supernatant of T cell cultures from protectively immunized donors contained substantial macrophage-activating factor whereas such activity was not detectable in the supernatant of T cell culture from s.c. immunized donors. Analysis by flow cytometry showed that the spleen and lymph nodes of normal, i.v., or s.c. immunized BALB/c mice contained similar ratios of L3T4+ cells and Lyt-2+ cells.

Animals↗
PubMed1987

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. I. Preferential inhibition of the induction of delayed-type hypersensitivity.

Culture supernatants of spleen cells from susceptible CBA mice chronically infected with Trypanosoma cruzi were able to inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens as measured by 24-hr footpad swelling, bone marrow homing, and radioactivity accumulation assays. The suppressive activity, which was also present in the serum of these chronically infected mice, appears to be specific for the induction of DTH and had no effect on the 3-hr immediate-type hypersensitivity. It also failed to modify the expression of DTH in presensitized mice. Furthermore, it did not affect the synthesis in normal recipients of specific antibody or the induction of helper T cells or cytotoxic T cells. It also failed to induce DTH tolerance as recipient mice with markedly reduced DTH were able to develop a normal DTH response after secondary immunization. The suppressive activity was produced by an Ig- macrophage-depleted splenic T cell population, whose capacity to secrete the suppressive substance was completely abrogated by treatment in vitro with anti-L3T4 antibody and complement, but not with anti-Lyt-2 antibody and complement. These results therefore demonstrate that L3T4+ T cells from mice chronically infected with T. cruzi can produce substances which interfere with the induction of DTH. This finding may help to identify the differential antigenic stimulatory requirement for the activation of the various subsets of T cells.

Animals↗
PubMed1987

Distinctive cellular immunity in genetically susceptible BALB/c mice recovered from Leishmania major infection or after subcutaneous immunization with killed parasites.

Genetically susceptible BALB/c mice are refractory to further infection after recovery from Leishmania major infection after a sublethal dose of gamma-irradiation. In contrast, mice immunized with killed promastigotes s.c. develop exacerbated lesions after infection. Both groups of mice produce only a low level of specific antibody and no detectable cytotoxic T cells, but do have a strong antigen-specific DTH, which is adoptively transferable with Lyt-1+2-, L3T4+ T cells. Kinetic and histological studies revealed that mice immunized s.c. developed Jones-Mote hypersensitivity, peaking at 15 hr. with little mononuclear cell infiltration at the site of antigen administration; whereas mice that had recovered from infection developed tuberculin-type of reactivity, peaking at 24 to 48 hr, with intense mononuclear cell infiltration. Splenic T cells from recovered mice, when injected into the footpads of normal recipients together with live promastigotes, were able to retard lesion development; whereas T cells from s.c. immunized mice, when similarly transferred, accelerated disease progression. Antigen-specific culture supernatant of spleen cells from recovered mice also activated normal resident peritoneal macrophages to kill intracellular L. major amastigotes and tumor cells. Culture supernatants of spleen cells from s.c. immunized or normal mice were devoid of such activities. Part of the macrophage-activating potential can be inhibited by antibody specific for IFN-gamma. These results therefore demonstrate that whereas the Jones-Mote reaction is correlated with disease exacerbation, the tuberculin-type of DTH may be protective. Furthermore, in vivo immunity is directly related to the capacity of T cells to produce macrophage-activating factor.

Animals↗
PubMed1987

Is there an interleukin 2 inhibitor in human serum?

Normal mouse serum has been shown to contain an inhibitor of interleukin 2 (IL-2). Here we report that a molecule with similar activity cannot be found in normal human serum (NHS). Although NHS inhibited the IL-2-dependent proliferation of mouse CTLL cells, as expected of an IL-2 inhibitor, it also had inhibitory activity on IL-3-dependent cells and was cytolytic to IL-2-independent mouse cells as measured by a 51Cr release assay, indicating a nonspecific effect. In addition, NHS had no effect on the IL-2-dependent proliferation of human peripheral blood T-cell blasts. Fractionation of NHS by size exclusion HPLC failed to separate cytolytic activity from any putative true IL-2 inhibitor activity. The cytolytic component was not related to immunoglobulin since it had a molecular weight of 50,000 to 60,000 and was not bound by protein-A-Sepharose. However, its molecular weight, heat lability, and trypsin sensitivity suggest it to be a protein.

Blood Proteins↗
PubMed1987

Regulation of cell-mediated immunity in cutaneous leishmaniasis.

There is now good evidence that cell-mediated immunity (CMI) rather than humoral antibody plays a causal role in acquired immunity to leishmaniasis. In genetically susceptible strains of mice, the failure to control the disease progression is associated with a population of Lyt-2-T cells which can prevent the induction or expression of curative CMI and hence exacerbate disease development. Susceptible BALB/c mice can be rendered resistant to L. major infection by prior sublethal dose gamma-irradiation, anti-mu antibody treatment from birth, anti-L3T4 antibody treatment or intravenous (i.v.) or intraperitoneal (i.p.) route of immunisation with killed L. major promastigotes or isolated leishmanial antigens. The route of immunisation, however, appears crucial in the induction of prophylactic immunity. Subcutaneous (s.c.) and intramuscular routes of immunisation with killed promastigotes are not only ineffective, they induce a population of Lyt-2- L3T4+ T cells which inhibit the prophylactic effect of i.v. immunisation. Although both the disease-promoting T cells and the host-protective T cells express the same phenotypic cell surface markers, they differ functionally. Protective T cells produce interferon-gamma (IFN-gamma) and macrophage-activating factor (MAF) when cultured in vitro with leishmanial antigens, whereas the disease-promoting T cells do not. In addition, these latter cells are able to produce substances in their antigen-specific culture supernatant which inhibits the MAF activity of the host protective T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems.

We investigated the ability of Salmonella typhimurium vaccines to deliver heterologous antigens to the systemic and secretory immune systems of the mouse, while retaining their immunogenicity against salmonellosis. S. typhimurium SL3261, an avirulent aroA mutant, or SL3261 carrying plasmid pBRD026, a pBR322 derivative encoding the gene for Escherichia coli LT-B were used to immunize BALB/c mice orally. Both immunizing strains invaded the mononuclear phagocyte system of the mice, grew slowly until approximately day 14 post-infection, and then were rapidly cleared. No salmonellae were detected in livers, spleens, mesenteric lymph nodes or Peyer's patches by day 42. Mice immunized with either strain and challenged orally with the virulent parent strain, SL1344, several weeks after clearing the immunizing organism, were protected against the lethal S. typhimurium infection. Mice infected with SL3261 (pBRD026) developed substantial levels of IgG and IgA anti-LT-B antibodies 14 days post-infection in both serum and gut samples. The sera neutralized the effects of LT in an in vitro Vero cell assay. Thus, aroA mutants of S. typhimurium can deliver a heterologous antigen from a different enteric pathogen to the murine systemic and secretory immune systems without altering their efficacy against salmonellosis.

Animals↗
PubMed1987

The initial suppression of bacterial growth in a salmonella infection is mediated by a localized rather than a systemic response.

Mice were infected intravenously with two antibiotic resistance tagged variants of the same S. typhimurium strain given in close succession, or simultaneously with strains of different virulence. The first manifestation of acquired resistance--suppression of exponential bacterial growth in liver and spleen--occurred independently for the different strains in the same individuals, implying that it is due to localized rather than systemic events. This early suppression of bacterial growth was ablated by whole body X-irradiation (800R), whereas the immediately preceding phase of exponential growth (Ity controlled innate resistance) was not affected. Transfer of spleen cell suspensions from infected mice into syngeneic recipients conferred protection by suppressing the growth of an intravenous challenge. Pre-treatment of the suspensions to deplete them of macrophages abolished their protective capacity, while depletion of T-cells did not. Mice deficient in T-cells by adult thymectomy and anti-T-cell monoclonal antibody treatment were able to suppress the growth of an intravenous challenge. Taken collectively, the present data show that the very early phase of acquired resistance to salmonellae, essential for survival, is not the result of systemically developing resistance but a localized event at the site of infection.

Animals↗
PubMed1987

Induction of delayed-type hypersensitivity to Leishmania major and the concomitant acceleration of disease development in progressive murine cutaneous leishmaniasis.

BALB/c mice injected intradermally with 10(5) or higher doses of formaldehyde-fixed promastigotes (FFP) of Leishmania major developed strong delayed-type hypersensitivity (DTH) to leishmanial antigens injected into the hind footpad 3 to 10 days later. The DTH peaked 15 to 18 h after footpad injection and disappeared by 48 h. This specific DTH correlated with the homing of 51Cr-labeled syngeneic bone marrow cells and the infiltration of proliferating cells to the site of antigen administration. Spleen cells from FFP-sensitized mice also gave significant proliferative response to FFP in vitro. The DTH was adoptively transferable by Lyt-1+2-L3T4+ T cells and was H-2 restricted. DTH could be substantially enhanced by pretreatment with cyclophosphamide or pertussigen. Such DTH enhancement was accompanied by concomitant exacerbation of disease progression after L. major infection. Mice injected intravenously with FFP developed substantial immunity to cutaneous leishmaniasis but specifically suppressed DTH reactivity. Treatment of mice with pertussigen before intravenous immunization, however, abolished the protection and reversed the suppression of DTH. These results therefore demonstrate that the early-appearing type of DTH is not involved in host protection but that it actually facilitates disease progression in cutaneous leishmaniasis. Further evidence, which also shows the nonspecific nature of this disease exacerbation, is provided by local cell transfer experiments. Splenic T cells from mice sensitized to keyhole limpet hemocyanin or FFP induced significantly larger lesions compared with normal T cells when they were transferred into the footpad together with specific antigen and L. major promastigotes.

Animals↗
PubMed1986

Cell-mediated immunity in experimental cutaneous Leishmaniasis.

Forms of cutaneous leishmaniasis are caused by Leishmania major, L. tropica, L. mexicana, L. amazonensis and L. panamensis. Like all leishmanial species, these are obligate intracellular parasites of the mononuclear phagocyte system, with a restricted range of vertebrate hosts including humans, dogs, rodents and arboreal animals. The disease evolves chronically, usually with slow healing, but can sometimes become nonhealing, diffuse disseminating or relapsing. The parasite exists within the macrophages of the vertebrate host in the amastigote form. These transform into extracellular flagellated promastigotes in the gut of the sandfly vectors. The promastigotes can then be injected into new vertebrate hosts as the insects feed. Promastigotes, and to a lesser extent amastigotes, can now be grown in tissue culture. This, together with the use of inbred mouse strains that are susceptible to most of the Leishmania species which are pathogenic for man, has facilitated great advances in our understanding of the immunological control of leishmaniasis. However, as Eddy Liew points out, there are still many unanswered questions.

Journal Article↗
PubMed1986

In vivo properties of a cloned K88 adherence antigen determinant.

An Escherichia coli strain of serotype O9:K36:H19 harboring the K88 recombinant plasmid pMK005 was able to efficiently colonize the small bowel of young piglets after oral infection. The strain expressed K88 antigen in vivo, and bacteria were detected in close association with the surface of the intestinal villi. Mice infected orally or intravenously with attenuated Salmonella typhimurium SL3261 harboring pMK005 were well protected against subsequent challenge with the highly virulent S. typhimurium SL1344. Anti-K88 antibodies were detected in the serum of mice immunized with SL3261(pMK005).

Adhesins, Escherichia coli↗
PubMed1986

Suppression of interleukin-2 production by macrophages in genetically susceptible mice infected with Leishmania major.

Spleen cells from BALB/c mice infected with 2 X 10(7) L. major promastigotes and developing progressive disease produced significantly lower levels of interleukin-2 (IL-2) in response to concanavalin A stimulation than did spleen cells from uninfected mice. In contrast, spleen cells from sublethally irradiated and infected mice, which were able to contain lesion development, produced significantly higher levels of IL-2. The increase in IL-2 production closely paralleled lesion regression. Mice protectively immunized by four intravenous injections with lethally irradiated promastigotes also produced enhanced levels of IL-2, which were sustained after challenge infection. In contrast, spleen cells from BALB/c mice given four s.c. injections of irradiated promastigotes produced high levels of IL-2 before but not after infection. These mice eventually produced levels of IL-2 indistinguishable from those of unimmunized mice with progressive disease. There is thus an inverse relation between disease progression and the ability of spleen cells to produce IL-2. Spleen cells from mice with uncontrolled disease not only produced lower levels of IL-2 but also impaired IL-2 production by normal spleen cells. The ability to inhibit IL-2 was abrogated by passing the cells through a Sephadex G-10 column, removal of plastic adherent cells, and removal of carbonyl iron-ingesting cells. Furthermore, Sephadex G-10 column-treated and plastic adherent, nonspecific esterase-positive spleen cells from mice with progressive disease were able to suppress IL-2 production by normal splenic T cells. The suppressive activity of the adherent cells was not affected by treatment with anti-Thy-1.2 antibody and complement. In contrast, adherent spleen cells from uninfected mice were devoid of such suppressor activity. The depressed IL-2 production by spleen cells from progressively infected mice could be restored to that of normal spleen cells by the addition of indomethacin to the culture. There was however, no correlation between IL-2 production and IL-1 activity in infected or immunized BALB/c mice. Thus, it appears that the suppression of IL-2 production is mediated by prostaglandins elaborated by macrophages from chronically infected mice.

Animals↗
PubMed1985

Helper T cells induced by an immunopurified herpes simplex virus type I (HSV-I) 115 kilodalton glycoprotein (gB) protect mice against HSV-I infection.

Three herpes simplex virus type I (HSV-I) glycoproteins of apparent molecular masses 103, 63, and 115 kD have been purified using virus-specific monoclonal antibodies (mAb) G8D1, C2D2, and T157, respectively. Both G8D1 and C2D2 neutralize HSV-I in vitro and passively protect CBA mice against HSV-I infection in vivo, whereas T157 is neither neutralizing nor passively protective. However, mice given a single subcutaneous injection of 30 micrograms 115 kD glycoprotein in saline were completely protected against lethal challenges of HSV-I administered intraperitoneally or in the footpad 7 d after immunization. In contrast, mice similarly immunized with 103 or 63 kD glycoproteins were only partially protected. The prophylactic immunity was correlated with an early induction of specific antibody, which became even more evident 3 d after virus challenge. There was a remarkable similarity in antibody isotype distribution between the responses to 115 kD glycoprotein and to heat-inactivated intact HSV-I. However, the prechallenge sera from 115 kD glycoprotein hyperimmunized mice were again neither virus-neutralizing nor passively protective. All three glycoproteins induced only low levels of delayed-type hypersensitivity (DTH). Pretreatment of mice with cyclophosphamide significantly enhanced DTH to 115 kD and 103 kD glycoproteins in the absence of antibody, but failed to confer significant immunity, indicating that DTH alone is insufficient for protection. Splenic and lymph node Ig- (B cell-depleted) cells from mice protectively immunized with 115 kD glycoprotein could adoptively transfer effective protection and enhance a virus neutralizing antibody response in normal recipients challenged with a lethal dose of HSV-I. Both the protection and the ability to enhance neutralizing antibody were diminished when the cells were treated with mAb GK 1.5 and complement. These results therefore demonstrate that the 115 kD glycoprotein, though not apparently containing accessible epitopes for the induction of virus-neutralizing antibody, possesses determinants capable of activating helper T cells. These L3T4+ cells confer strong protective immunity by enhancing protective antibody upon challenge infection, probably through associative help.

Animals↗