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Biomedical subjects

F Y Liew

Publications and source records attributed to F Y Liew.

At least 217 records · Page 12Linked to original sources
PubMed1982

Regulation of delayed-type hypersensitivity. VI. Antigen-specific suppressor T cells and suppressor factor for delayed-type hypersensitivity to histocompatibility antigens.

Mice develop highly significant levels of delayed-type hypersensitivity (DTH) to major and minor histocompatibility antigens when injected s.c. with lymphoid cells from X-irradiated allogeneic donors. However, when mice are inoculated i.v. with a high dose of X-irradiated allogeneic lymphoid cells, they not only fail to develop DTH to the allogeneic cells, but their ability to respond to an immunogenic challenge of the alloantigens is also significantly depressed. This suppression is adoptively transferable by antigen-specific suppressor T cells and not by immune serum. Cell surface phenotypic analysis shows that the primary suppressor cells for alloantigens are Thy-1+, Lyt-1+2-, and Ia-, whereas the secondary suppressor cells appearing after boosting injection are Thy-1+, Lyt-1+2+, and Ia-. These suppressor T (Ts) cells localize in the lymphoid organs shortly after their induction and are largely absent from the spleen or lymph node 1 month later. However, "suppressor memory" can be recalled by an immunogenic dose of alloantigens which would normally induce DTH effector cells rather than suppressor cells in naive mice. When the suppressor cells were cultured in vitro for 48 hr, the supernatant contained suppressive activity. It appears likely that the manifestation of the suppressor cells is via soluble, antigen-specific suppressor factor(s), the production of which is dependent on viable T cells.

Animals↗
PubMed1981

Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica.

The overwhelming susceptibility of BALB/c mice to infection with Leishmania tropica can be substantially reversed by immediately prior sub-lethal irradiation. This is related to radiation dosage, and at 550 rad, causes 60 percent complete cures and only 19 percent (instead of 100 percent) incidence of progressive disease. Irradiation 10 d before infection is only weakly prophylactic, whereas 10 d after is without effect. Control of lesion development is only apparent after the first 30 d, coincident with the analogous onset previously found in resistant strains and adult thymectomized, x-irradiated, bone marrow-reconstituted BALB/c mice. Instead of the specific suppression of DTH characteristic of L. tropica infection in the BALB/c strain, healed irradiated mice express strong anti-leishmanial DTH reactivity and resistance to reinfection. T cells from these mice transfer DTH reactivity which is suppressed by admixture with cells from nonhealed, nonreactive donors. Irradiated BALB/c mice again develop inexorable disease progression, after its transient arrest, when they are reconstituted with normal T cells. When the T cells are derived from uncontrollably-infected donors, the susceptibility regained is indistinguishable from that of normal mice. B cells do not modify the prophylactic effect of 550 rad, whereas T cells from healed mice confer strong protective immunity throughout the initial phase. Regression or progression of disease correlates completely with DTH reactivity in all these groups. Although BALB/c mice express an extreme level of genetic susceptibility to L. tropica infection, they are nevertheless capable of mounting a curative cell mediated immune response. That this is ineffective during pathogenesis of the disease was previously associated correlatively with potent specific suppressor T cell generation, which is now shown to be preventable by prior irradiation. Most important, however, a causal role for these cells in vivo has been demonstrated directly by reconstitution.

Animals↗
PubMed1981

Regulation of delayed-type hypersensitivity. VII. The role of I-J subregion gene products in the inhibition of delayed-type hypersensitivity to major histocompatibility antigens by specific suppressor T cells.

Suppressor T cells for delayed-type hypersensitivity (DTH) to alloantigens are induced by injecting mice intravenously with a high dose of X-irradiated allogenic cells. Using the same protocol, suppression of DTH directed against H-2 subregion products could also be induced, provided that the H-2 incompatibility between the cells used for the induction of suppression and the recipients includes the I-J subregion genes. Thus, the I-J subregion difference is both necessary and sufficient for the induction of suppression of DTH to the whole or part of the H-2 gene products. The suppression appears to be mediated by antigen-specific suppressor T cells which recognize the allo-I-J molecules and are able to suppress the DTH response to other H-2 subregion gene products in an associative recognition manner. T cells from (B10 x BALB/c)F1 mice suppressively primed against B10.A(5R) cells (directed against JkEk antigens), when adoptively transferred to normal syngeneic recipients, were capable of suppressing the hosts' DTH response to B10.A(4R) cells (KkAk antigens) when the recipients were challenged with [B10.A(4R) x B10.A(5R)]F1 cells (KkAk x JkEk). The recipients express normal DTH reactivity to B10.A(4R) cells when challenged with a mixture of B10.A(4R) cells (KkAk + JkEk). These results provide direct evidence that when functioning as alloantigens, the I-J determinants preferentially induce suppressor T cells which specifically impair the immune response to the I-J molecules as well as other H-2 gene products if they are physically associated with the I-J determinants. The role of I-J subregions as the suppressor genes is discussed in terms of the possible application in transplantation immunity and the host's defence against infectious diseases.

Animals↗
PubMed1981

Induction of delayed-type hypersensitivity to Mycobacterium leprae in healthy individuals.

Delayed-type hypersensitivity (DTH) to a soluble Mycobacterium leprae skin test antigen (SML) was successfully induced in healthy volunteers following immunization with 2 X 10(8) killed armadillo-derived M. leprae. No better sensitization was obtained by a mixture of live BCG and killed M. leprae. The relative specificity of the DTH reaction to SML has been demonstrated in this study, since little cross-reactivity was observed to PPD, after immunization with BCG ro M, leprae alone, or combined. Moreover, armadillo-derived M. leprae readily induced a specific hypersensitivity with the time course DTH response associated with protective immunity suggesting that this bacterial preparation may be a candidate for an effective anti-leprosy vaccine.

Adolescent↗
PubMed1981

Failure to induce delayed-type hypersensitivity to Mycobacterium leprae in long-term treated lepromatous leprosy patients.

Lepromatous leprosy (LL) patients whose bacillary load has decreased to almost undetectable levels by long-term chemotherapy failed to develop delayed-type hypersensitivity (DTH) to Mycobacterium leprae antigen following immunization with killed armadillo-derived M. leprae. When these LL patients were immunization with killed armadillo-derived M. leprae. When these LL patients were immunized with killed M. leprae in a mixture with live BCG, only DTH to purified protein derivative (PPD) was induced. These results are further evidence that immunological unresponsiveness to the leprosy antigen of patients with lepromatous leprosy is antigen-specific and non-reversible.

Antigens, Bacterial↗
PubMed1980

Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica.

BALB/c mice have been an exceptional susceptibility to Leishmania tropica infection such that cutaneous lesions grow without restraint in all cases leading to fatal metastasis and visceralization in normal and x-irradiated, bone-marrow reconstituted (XBM) animals. Adult thymectomized, x-irradiated, bone marrow-reconstituted (ATxXBM) BALB/c mice, however, show pronounced retardation of lesion growth leading to some survival and even cures. A similar trend was also found in moderately susceptible (BALB/c X C57BL/6)F1 mice, in contrast with the "resistant" CBA strain, in which, as previously known, ATxXBM animals showed impairment of normal, spontaneous self-healing. These convere effects are paralleled by respective leishmania-specific delayed-type hypersensitivity (DTH) reactivities, prior thymectomy leading to diminution in CBA and augmentation in BALB/c and (BALB/c X C57BL/6)F1. Anti-leishmanial DTH responses, amplfiable by cyclophosphamide pretreatment, can be detected in BALB/c mice within 10 d of infection with 2 X 10(7) promastigotes, but becomes near-totally suppressed by day 25-35. No such suppressin is found in CBA, C57BL/6, or (BALB/c X C57BL/6)F1 mice together with varying degrees of immune control of lesion development or regression. Suppression of DTH in BALB/c mice is leishmania specific and does not extent to 2,4-dinitrofluorobenzene (DNFB) or sheep erythrocytes specificities. Spleen cells from suppressed L. tropica-infected mice when transferred to normal BALB/c mice impaired the induction of DTH to leishmanial antigen. This property resided in the T cell-enriched fraction and not in the T cell-depleted fraction. It is concluded that a major component of the striking inability of BALB/c mice to control L. tropica infection involves profound impairment of a potentially curative cell-mediated immune response by suppressor T cell generation. The possibility is discussed that this may be secondary to rapid amastigote (antigen) accumulation in macrophages expressing the primary genetic "defect."

Animals↗
PubMed1980

Delayed-type hypersensitivity to influenza virus. Induction of antigen-specific suppressor T cells for delayed-type hypersensitivity to hemagglutinin during influenza virus infection in mice.

Mice infected with A/England/939/69 X A/Puerto Rico/8/34 (Rec 31) influenza virus by aerosol develop significantly lower levels of delayed-type hypersensitivity (DTH) to A/Hong Kong/1/68 X A/Puerto Rico/8/34/ (X31) virus compared to uninfected mice. The suppression of DTH to the hemagglutinin appears to be mediated by suppressor T cells which carry Lyt-1 membrane antigen marker, and not by sy serum antibody. The suppressor T cells for DTH induced by Rec 31 virus (H3N1) infection suppress the DTH response to the variants of the H3 subtype of influenza viruses, but have no effect on the DTH responses to A/Puerto Rico/8/34 virus (H0N1), a B influenza virus or the matrix protein of type A influenza virus. Suppressor T cells for DTH appear 2 wk after infection and are detectable in the spleen for at least 40 d thereafter. T-helper cells for antibody response to hemagglutinin are induced concomitantly with the T-suppressor cells for DTH. Possible implications of the present findings on the regulation of the immune response to viral infection are discussed.

Animals↗
PubMed1980

Major histocompatibility gene complex (MHC)-coded determinants on antigen-specific suppressor factor for delayed-type hypersensitivity and surface phenotypes of cells producing the factor.

Antigen-specific suppressor factor for delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was obtained by incubating in vitro spleen cells from CBA mice (H-2k) injected intravenously 3 days previously with 1 x 10(9) SRBC. The suppressor factor was characterized for major histocompatibility gene complex (MHC)-coded antigenic determinants by passing the factor through immunosorbents coupled with appropriate alloantisera. The suppressor factor was absorbed by anti-H-2k, anti-Iak and anti-I-Jk immunosorbents but was not retained by anti-Ias, anti-I-Js, anti-I-Ak, anti-I-E/Ck or anti-H-2Kk immunosorbents. In addition, the factor bound to an immunosorbent coupled with rabbit antibodies against carbohydrate-defined Ia antigens. Furthermore, the suppressive activity that was absorbed was quantitatively recovered in the acid eluates from the immunosorbents. Treatment of the spleen cells with anti-Lyt-1.1 antiserum and complement completely abrogated their ability to elaborate the suppressor factor in vitro. In contrast, treatment with anti-Lyt-2.1 or anti-Iak antiserum and complement had no effect. Thus, it appears that the suppressor factor for DTH to SRBC bears I-J subregion-coded determinants, and its production is dependent on cells which have the Lyt-1+,2- and Ia- phenotype.

Animals↗
PubMed1980

Cell cooperation in antibody responses to influenza virus. I. priming of helper t cells by internal components of virion.

T cells recognizing internal components of the influenza virion can cooperate with B cells recognizing hemagglutinin to enhance the hemagglutinin inhibition (HAI) antibody response. Cooperation occurs only when the internal proteins and hemagglutinin are subsequently presented in association. The effect enhances the production of both 2-mercaptoethanol-resistant and -sensitive antibodies. The cooperating cells express the Thy-1+, Ly-1+2- surface phenotype and thus are characteristic of helper T cells. Immunization of mice with the internal components of the virion increases survival after exposure to lethal influenza infection. Mice primed with purified matrix protein produce enhanced amounts of HAI antibody after infection with influenza. These results may help to explain reports on the effects of heterotypic infection on antibody production, and also heterotypic immunity.

Animals↗
PubMed1980

Regulation of delayed-type hypersensitivity. V. Suppressor cell memory in antigen-specific suppression of delayed-type hypersensitivity to sheep erythrocytes.

Mice printed i.v. wit 10(9) sheep red blood cells (SRBC) produce antigen-specific T suppressor (Ts) cells which inhibit both the induction and the expression of delayed-type hypersensitivity (DTH). These Ts cells are detectable in the spleen and lymph nodes 3-5 days after priming but are largely absent by 6 days. The transient detectability of the Ts cells contrasts sharply with the profound antigen-specific suppression which persists in primed donor mice for at least a year. Evidence is presented that this long-term impairment of DTH is maintained, at least in part, by memory Ts cells which are Thy-1+, cyclophosphamide-resistant and antigen-specific. Although they appear to be co-induced with the short-lived primary Ts cells and localize initially in the lymphoid organs, they are present in the long-lived circulating pool of T cells and can be adoptively transferred by celomic parabiosis. Memory Ts cells are readily reactivated by lower doses of SRBC which would induce T effector cells rather than Ts cells in naive animals. Reactivated memory Ts cells seem to generate a population of antigen-specific secondary Ts cells which again localizes in the lymphoid organs and can adoptively suppress the induction and expression of DTH to SRBC.

Animals↗
PubMed1980

Delayed-type hypersensitivity responses to H-Y: characterization and mapping of Ir genes.

This paper examines the delayed-type hypersensitivity (DTH) response to male (H-Y) antigen(s). Female mice of the H-2b haplotype developed delayed footpad reaction to syngeneic or allogenic male thymus and spleen cells after priming with syngeneic male thymus and spleen cells. The reaction peaks at 24 h, has classical DTH histology and is specific to H-Y antigen as it is not elicited with female cells. Cell transfer studies show that donor/recipient matching at the I-Bb subregion is necessary for successful transfer of DTH and that the effective primed population is Thy-1+, Lyt-1+, 2-. DTH response to H-Y antigen appears to be confined to mice of the H-2b haplotype. There appears to be a lack of associative recognition between H-Y antigen and MHC-coded determinants in the effector phase of DTH, and macrophage processing of H-Y seems likely, since nonresponder haplotypes can elicit the DTH response. Studies with H-2b recombinant mouse strains indicate that the dominant Ir gene is located in the I-B region. Female F1 hybrid mice derived from matings of strains not involving H-2b haplotype failed to develop DTH to H-Y. In summary, these data imply that a complete correlation exists between DTH to H-Y and the ability to reject male skin graft, suggesting that the effector mechanisms of skin-graft rejection may closely involve DTH cells.

Animals↗
PubMed1979

Regulation of delayed-type hypersensitivity IV. Antigen-specific suppressor cells for delayed-type hypersensitivity induced by lipopolysaccharide and sheep erythrocytes in mice.

Mice injected subcutaneously with 1 x 10(8) sheep red blood cells (SRBC) developed high levels of delayed-type hypersensitivity (DTH) to SRBC 4-8 days after injection. Such DTH was suppressed when 100 microgram lipopolysaccharide (LPS) was injected intravenously 1-2 days before or at the time of SRBC injection. This suppression of DTH was transferable by spleen, lymph node, thymus and bone marrow cells to sensitized or normal syngeneic recipients, but could not be transferred by serum. Suppressor cells were not induced by LPS alone or SRBC alone, and they were antigen-specific since DTH to chicken red blood cells was not affected. The suppressor cells appeared in the spleen in optimum number 3-4 days after induction. They were theta-negative and Ig-positive as judged by antiserum plus complement treatment and by Ig rosette separation. Attempts to obtain soluble suppressor factor from the suppressor cells by sonication or in vitro incubation were unsuccessful. Mitomycin C treatment of the suppressor cells completely abolished the suppressor activity. Thus, LPS, in conjunction with antigen, appears to induce a population of specific suppressor B cells which are capable of regulating T cell function.

Animals↗
PubMed1979

Antigen-specific suppressor factors produced by T cell hybridomas for delayed-type hypersensitivity.

This study describes the generation of T hybridoma lines which secret factors specifically suppressing delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC). AKR strain-derived T lymphoma BW 5147 cells were fused with spleen cells from mice primed with SRBC and containing antigen-specific T suppressor cells for DTH. Supernants from the derived hybridomas were tested for suppression of either expression of induction of DTH to SRBC. Six lines produced specific suppressor activity for the expression of DTH; 4 lines produced suppressor activity for the induction of DTH of which only one line was antigen-specific. These lines were passaged in normal AKR mice, and the serum obtained had activity up to 10(-4) dilution. The factor was effective across the H-2 barrier.

Animals↗
PubMed1979

Dissociative effects of malarial infection on humoral and cell-mediated immunity in mice.

The effect of malarial infection on immune responses was studied in mice. When sheep red blood cells (SRBC) were injected 2 days before or at the same time as infection with Plasmodium berghei, there was a marked increase in the number of splenic plaque forming cells (PFC) induced by SRBC as compared with uninfected controls. When SRBC were injected 2 days or more after the infection, however, the PFC response was significantly reduced. On the other hand, cell-mediated immunity, as exemplified by delayed-type hypersensitivity (DTH) to a number of antigens, was suppressed whether the infection was introduced before or after antigen stimulation. A similar effect could be produced by injecting the host with the supernatant obtained following incubation in vitro of peripheral blood from heavily infected mice. When this supernatant was injected i.v. into normal mice at the same time as SRBC priming, it enhanced the humoral response to SRBC, but suppressed the DTH to SRBC. The coincident induction of this inverse relationship between humoral and cell-mediated immunities was clearly borne out by a dose response study using different dilutions of supernatant. The active component appeared to be of large molecular weight (greater than 150,000), thermostable and not present in the serum of infected mice.

Animals↗