Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly susceptible naive BALB/c mice or mice that had previously been immunized i.v. with solubilized homologous antigen (partially resistant) were infected with Leishmania amazonensis. Histologically, the main differences between the two groups were lymphocytic infiltration and macrophage activation. Assays of T-cell function at 3 and 10 weeks after infection revealed that purified T-cells did not proliferate following treatment with leishmania antigen. A mitogenic anti-CD3 monoclonal antibody (mAb) failed to activate T-cells after 3 weeks of infection as judged by proliferation and IL-2 secretion assays. After 10 weeks of infection, anti-CD3 mAb fully activated T-cells to proliferation and IL-2 secretion. On the other hand, T-cells released IL-3 in response to leishmania antigen, anti-CD3 mAb and anti-Thy1 mAb at 3 and 10 weeks post-infection. Surprisingly, a mitogenic anti-Thy 1 mAb (G7) fully activated T-cells even at 3 weeks of infection as judged by proliferative and IL-2 secretion assays. No significant differences were found in the proliferative or interleukin secretory responses of T-cells from animals that had been infected in either the presence or the absence of prior immunization. Since the Thy1 triggering pathway has different accessory cell and cytokine requirements than does the CD3: TCR lymphocyte activation pathway, it is possible that immunization was more effective in changing the cellular interactions of the T-lymphocyte than in altering its intrinsic capabilities.
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PMID:T-lymphocytes in experimental Leishmania amazonensis infection: comparison between immunized and naive BALB/c mice. 158 41

A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2+, Lyt2+, L3T4- phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. We suggest that the release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors.
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PMID:[Formation of specific antitumor cytotoxic T-lymphocytes in monoculture]. 161 Oct 71

To determine cell-mediated immune mechanisms involved in the resolution of chlamydial genital infection of mice, we utilized an established murine model in which it has been demonstrated that resolution of infection occurs independently of the antibody response. Splenic T lymphocytes were obtained from mice that had previously been immunized with viable elementary bodies of the mouse pneumonitis agent (MoPn), a Chlamydia trachomatis biovar. Antigen-reactive T lymphocytes were maintained and expanded in vitro by frequent restimulation with UV light-inactivated MoPn in the presence of antigen-presenting cells and recombinant interleukin-2 (rIL-2). Flow cytometry indicated that this cell line was at least 92% positive for the pan-specific T-cell marker Thy1.2. Stimulation of the cells in the presence of syngeneic antigen-presenting cells plus MoPn antigen and in the absence of exogenous IL-2 induced the cells to produce IL-2 activity in culture supernatants. Following adoptive transfer, this T-lymphocyte line was effective in inducing resolution of an ongoing MoPn genital infection in congenitally athymic nude mice which otherwise maintain chronic unresolved infections. The line was less efficient in resolving the infection after longer periods in culture. An additional T-lymphocyte line was derived from the spleens of athymic mice that had received the first line and had resolved the infection. These T cells were also capable of inducing resolution of the infection. Lastly, this cell line was treated with specific antibody and complement to delete either CD4+ or CD8+ T lymphocytes in an attempt to enrich for T-cell subpopulations prior to transfer into infected athymic mice. The anti-CD4-treated line was essentially depleted of CD4 cells, while the anti-CD8-treated line was only partially enriched for CD4 cells, with a large proportion of CD8 cells still present. Nude mice that received either of the treated T-cell lines or the parental cell line were capable of resolving the infection, although the line with increased numbers of CD4 cells was more efficient than either the parental line or the CD8 line.
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PMID:Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. 170 44

Specific antitumor effects of lymphokine activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Furthermore, effects of preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 were clinically studied against gastric cancer. The results were as follows: After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. 1) Adoptive transfer of the effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 2) The analysis of the surface antigens indicated the Thy1.2, Thy1.2+ L3T4+ cells increased in the effector cells as the specific cytotoxicity of them were augmented. 3) Preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 induced immunocytes including antigen-presenting cells in the site of the gastric cancer, and increased the IL-2R and the LAK activity of PBL. This method was considered as effective as an adjuvant treatment of gastric cancer surgery as a in vivo sensitization.
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PMID:[Intratumoral injection of biological response modifier (BRM)]. 194 92

Specific antitumor effects of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Inbred C57BL/6 mice bearing syngeneic tumor (B16,3LL) were used. After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. Specific antitumor effects of the effector cells against B16 and 3LL were studied in vitro and in vivo. Surface antigens of them were also analysed. The results were as follows: 1) 51Cr-release test under coculture with rhIL-2 showed that cytotoxicity against the host tumor cells with the effector cells became specifically augmented. 2) Winn assay showed specific inhibition of the host tumor growth with the effector cells. 3) Adoptive transfer of te effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 4) The lymphokine-activated lymphocytes obtained from normal and non-treated tumor-bearing mice had no specific antitumor effect. 5) The analysis of the surface antigens indicated that Thy1.2+L3T4+ T cells increased in the effector cells as the specific cytotoxicity of them were augmented, while in the effector cells from normal and non-treated tumor-bearing mice, Thy1.2+L3T4+ T cells decreased and Thy1.2+Lyt2+ T cells increased.
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PMID:[Specific antitumor effect of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of interleukin-2 (IL-2)]. 205 76

The development of methods of avoiding graft-versus-host disease (GVHD) while retaining the alloengraftment-promoting and anti-leukemic effects of allogeneic T cells is a major goal of research in bone marrow transplantation (BMT). We have recently obtained evidence suggesting that natural suppressor (NS) cells derived from T cell-depleted (TCD) syngeneic marrow can protect against GVHD while permitting alloengraftment. We have now attempted to enrich and then propagate NS cells in vitro, with the goal of obtaining an enhanced anti-GVHD effect by adoptive transfer in vivo. Two long-term cell lines were generated culturing BMC depleted of Mac1-positive cells and of Mac1-positive plus Thy1-positive cells in high concentrations of IL-2. Both cell lines showed anti-GVHD effects when administered along with a GVHD-producing inoculum, while permitting complete allogeneic reconstitution. A clone derived from Mac1-depleted BMC protected completely against a more chronic pattern of GVHD. These cell lines demonstrated suppressive activity in vitro, cytolytic activity against a broad range of natural killer (NK)-sensitive and NK-resistant targets, and a novel cell surface phenotype, with characteristics of both alpha beta-TcR-bearing T cells and of NK cells. In some respects, these cells resemble LAK cells and differ from fresh NS cells, and from the cloned NS cells derived from spleens of total lymphoid irradiation (TLI)-treated mice and neonatal mice. To our knowledge, this is the first detailed phenotypic analysis of cell lines with in vivo anti-GVHD activity. If applicability can be demonstrated in large animal models, the ability to use bone marrow as a source of such protective cell lines might also have potential utility in clinical BMT.
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PMID:In vitro and in vivo analysis of bone marrow-derived CD3+, CD4-, CD8-, NK1.1+ cell lines. 214 39

The role of cytotoxic T cells and NK cells in the recovery of immunodeficient, athymic, nude mice infected with a recombinant vaccinia virus (VV) encoding murine IL-2 was investigated. Kinetic studies with the IL-2-encoding recombinant (VV-HA-IL2) and control (VV-HA-TK) viruses excluded a role for cytotoxic T cells but suggested the possible involvement of NK cells. In athymic nude mice given VV-HA-IL2, NK activity was at least threefold higher than mice infected with VV-HA-TK and this activity persisted for at least 6 days after infection. The effectors mediating the NK-like activity were asialo-GM1+ (as-GM1+), Thy1.2+/-, CD4- and CD8-, the phenotype of conventional NK cells. Elevated NK activity coincided with the rapid clearance of VV-HA-IL2 from ovaries of infected normal CBA/H mice but not from ovaries of CBA beige mice which had no detectable NK activity in spleens or ovaries. The expression of IL-2 in recombinant VV infection probably induces a cascade of immunologic effects of which elevated NK activity is one. We speculate that the chemoattractant and NK activity augmenting effects of IL-2 may contribute to recovery from VV-infection.
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PMID:Elevated natural killer cell responses in mice infected with recombinant vaccinia virus encoding murine IL-2. 229 96

Studies were performed to determine the basis for low NK activity in the spleens of SJL/J mice. In contrast to substantial boosting by IL-2 or IFN of NK activity of spleen cells from high NK-reactive strains of mice, no detectable effect of these cytokines on SJL spleen cells was seen. When SJL spleen cells were cultured for 7 days in the presence of IL-2, the frequency of proliferating cells was comparable to that of other strains of mice. However, the SJL spleen cells showed a frequency of NK-cell progenitors which was at least 50 times lower than that of the CBA/J spleen cells. In addition to having no detectable effector-cell activity, the cultures of SJL spleen cells contained suppressor cells which were able to inhibit the NK activity of spleen cells from other strains of mice. These suppressor cells did not adhere to plastic or nylon wool and were found in low-density fractions after Percoll density gradient centrifugation. The cultured SJL spleen cells had a high percentage of cells capable of binding to NK-susceptible target cells, which was similar to that seen in lytic cultures from other strains of mice. Thus, the suppressor activity may be attributable to competitive inhibition of the interaction of effector cells with target cells. Although several of the characteristics of suppressor cells were similar to those of cultured effector cells, they may not represent inactive or pre-NK cells since their progenitors were Thy1+ and AsialoGM1- whereas the progenitors of cultured effector cells in high NK strains were Thy1- and GM1+. The ability to eliminate the progenitors of the suppressor cells by pretreatment of spleen cells with anti-Thy1 plus C' also suggested that the low or undetectable NK activity of the cultured SJL cells is not attributable to suppression but may be due to an inherent deficit of NK cells.
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PMID:Low frequency of NK-cell progenitors and development of suppressor cells in IL-2-dependent cultures of spleen cells from low NK-reactive SJL/J mice. 242 46

Transgenic mice carrying the human IL-2R alpha/p55 gene under the control of the SV40 enhancer/promoter were used to study the relevance of IL-2R in T-cell development. Serological analysis of the mouse lines obtained indicated transient, regulated expression of the human p55 gene, mainly confined to the early thymus, but which was also detected in lower amounts in the spleen. These mice showed degenerated thymuses, with an increased number of Thy1.2- double-negative precursor cells; they also had specific depletion of double-positive thymocytes. Transgene expression led to an increased number of intermediate-affinity IL-2 receptors (possibly ascribed to deregulated expression of IL-2R beta/p75) in transgenic thymocytes older than 12 weeks. These results suggest the occurrence of strong linkage between the IL-2/IL-2R system elements and thymic differentiation/maturation; they lend support to the idea of functionality of IL-2R expressed transiently in early stages of T-cell development.
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PMID:Analysis of T-cell subpopulations in human IL-2R alpha transgenic mice: expansion of Thy1.2- thymocytes and depletion of double-positive T-cell precursors. 257 90

The establishment of IL-2-independent T-cell lines spontaneously derived from long-term IL-2-dependent cytotoxic T-cell lines is described. Two lines (cloned and uncloned) studied in detail have shown the following characteristics: (1) Permanent loss of IL-2 dependence. (2) Partial or complete loss of both cytotoxic activity and the IL-2 receptor. (3) Increased expression of T-cell membrane markers (Thy1.2, Lyt1.2) compared with the parental line. (4) Lower level of DNA methylation than in freshly obtained lymphoid cells. (5) Different karyotypic pattern from the parental IL-2-dependent line, with a mean number of 39-40 chromosomes and a resemblance to T leukemic lines. (6) Leukemia caused in normal syngeneic C57BL/6 mice by the uncloned line, in contrast to the cloned IL-2-independent line or the parental dependent line. Unlike established leukemic lines, however, the independent line gave rise to tumors which regressed in some mice within a few days of their appearance. These findings suggest that T-cell lines maintained with IL-2 for prolonged periods of time (greater than 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes.
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PMID:Characterization of a tumorigenic murine T-lymphoid-cell line spontaneously derived from an IL-2-dependent T-cell line. 308 91


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