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)

We induced nonspecific killer cells in the local site of delayed-type hypersensitivity against keyhole limpet hemocyanin or ovalbumin. Delayed-type hypersensitivity was induced in the peritoneal cavities of mice, and peritoneal exudate cells (PEC) were collected. These PEC were found to have killer activity toward SP2 and YAC-1 cells (target cells susceptible to natural killer cells) by 4-h 51Cr-release assays. The induction of killer activity in PEC was observed in parallel with the eliciting of delayed-type hypersensitivity in the peritoneal cavity, in which the killer activity was maximum 24-48 h after the antigen challenge, but was not induced in nu/nu mice and was induced in an antigen-specific way. These killer cells did not adhere to nylon wool and had Thy1 and asialo-GM1 antigens on their surfaces. Their precursor cells were also asialo-GM1-positive. These findings indicate that the killer cells probably belong to the NK cell lineage. Results of tumor challenge experiments showed that these killer cells had an antitumor effect in vivo as well as in vitro.
Cancer Immunol Immunother 1989
PMID:Induction of nonspecific killer cells by delayed-type hypersensitivity against soluble protein antigens in murine peritoneal cavities. 256 10

We have previously demonstrated that incubation of murine cells in vitro in interleukin 2 (IL-2) induced antibody-dependent cellular cytotoxicity (ADCC) and that these cells were derived from the NK/LAK, FcR+ cell population. In the present study we show that in vivo administration of IL-2 to mice induces cells which exhibit ADCC activity in the peritoneal cavity, liver, lungs, and to a lesser degree in the bone marrow, spleen, mesenteric lymph nodes, and thymus. A gradual increase in ADCC activity and the number of Fc-receptor-positive cells was seen 1 to 3 days after starting IL-2 treatment. The cells mediating ADCC are closely related to LAK cells since they expressed Thy1.2 antigens and are derived from asialo GM1-positive, Lyt2/L3T4-negative, radiosensitive cells. These results demonstrate that IL-2 can systemically induce cells with ADCC activity and that this ability may be useful in the establishment of therapeutic models against disseminated cancer when combined with specific antitumor monoclonal antibodies.
Cancer Res 1989 Dec 15
PMID:Systemic induction of cells mediating antibody-dependent cellular cytotoxicity following administration of interleukin 2. 257 25

Metastasis can be inhibited by asialo-GM1-positive spleen cells, and in this paper we show that there are two such spleen cell populations. One population is adherent and non-cytotoxic to YAC cells, whereas the other population is non-adherent and cytotoxic to YAC cells. Both cell populations exert an antimetastatic activity in cyclophosphamide-treated mice that are inoculated with LL2 Lewis lung carcinoma cells. We conclude that the antimetastatic activity is not only exerted by cytotoxic asialo-GM1-positive cells (apparently natural killer cells), but also by adherent, non-cytotoxic asialo-GM1+, Thy1.2-, IgG- cells. This means that the latter exert their antimetastatic activity by a non-cytotoxic mechanism.
Cancer Immunol Immunother 1989
PMID:Non-cytotoxic asialo-GM1-positive cells exert antimetastatic activity. 259 76

The purpose of this study was to characterize the lymphocyte populations responsible for rejection of immunogenic (Imm+) tumor variants, and the cross-protective immunity engendered by Imm+ variants against the weakly immunogenic parental tumor. Immunogenic clones of the weakly immunogenic methylcholanthrene-induced fibrosarcoma MCA-F have been generated using 1-methyl-3-nitro-1-nitrosoguanidine, 5-aza-2'-deoxycytidine, or ultraviolet radiation (UV-B; 280-320 nm). These clones grow progressively in immunosuppressed adult-thymectomized irradiated mice, but are rejected by immunocompetent syngeneic hosts. The parental MCA-F tumor grows progressively in both groups. Mice that have rejected a challenge of 1 x 10(5) Imm+ cells show an anamnestic immune response against both the Imm+ clone and the parental MCA-F tumor. Using the local adoptive transfer assay and depletion of T-cell subsets with antibody plus complement, we show that immunity induced by the Imm+ variants against the parent MCA-F was mediated by the Thy1.2+, L3T4a+ population without an apparent contribution by Lyt2.1+ cells. Although antivariant immunity was also dependent upon Thy1.2+ cells, depletion of either the L3T4a+ or the Lyt2.1+ cells failed to abolish immunity against the variant. A role for Lyt2.1+ T lymphocytes in antivariant immunity, but not antiparent immunity, was supported by the results of cytotoxic T lymphocyte (CTL) assays. Following immunization with high numbers (1 x 10(5) to 5 x 10(5) of viable Imm+ cells, antivariant, but not antiparent CTL activity was detected in mixed lymphocyte tumor cell cultures. Immunization with lower numbers (3 x 10(4] of viable Imm+ or with high numbers of mitomycin-C-treated Imm+ engenders only antivariant immunity without parental cross-protection. Under these conditions lymphocytes mediating immunity against the variant in the local adoptive transfer assay were exclusively of the Thy1.2+, L3T4a+ phenotype, with no contribution from the Lyt2.1+ cells. Identical results were obtained for Imm+ clones of MCA-F induced by methylnitronitrosoguanidine, 5-azadeoxycytidine, and UV-B, suggesting that the nature of the antitumor immunity engendered by Imm+ is not significantly affected by the agent used. Furthermore, these results demonstrate that the cross-reactivity and cellular effectors of antitumor immunity in this system are influenced by the immunizing dose of Imm+ cells: the predominant effectors of both antivariant and parental-cross-reactive immunity were of the CD4+ T cell subclass, with a CD8+ cytotoxic population contributing to antivariant immunity only after high-dose immunization.
Cancer Immunol Immunother 1989
PMID:Characterization of variant and parental-cross-protective immunity to immunogenic variants of a murine fibrosarcoma using the local adoptive transfer assay. 259 91

Nonadherent cells of the bone marrow of C3H/HeN mice were incubated for 3 days with the culture supernatant of an L-929 cell line containing macrophage-colony-stimulating factor. Approximately, 70% of the cells became phagocytic, adherent to plastic dishes and positive for nonspecific esterase staining. The adherent cells exhibited a weak tumoricidal activity against syngeneic mammary carcinoma cells, and the cytotoxicity was strongly augmented by the addition of bacterial lipopolysaccharide to the cytotoxicity assay. The cytotoxicity induced by lipopolysaccharide was also shown to be mediated by Thy1.2- and asialo-GM1+ cells, and was abrogated by the addition of carrageenan. Macrophage-colony-stimulating-factor-producing (D66) and nonproducing (A23) variants were separated from the MM48 tumor line in in vitro culture following limiting dilution. There was no difference between these two variants in either the in vitro growth rate or the susceptibility to macrophage-mediated cytotoxicity. C3H/HeN mice inoculated i.p. with D66 survived longer than did those inoculated i.p. with A23. C3H/HeN mice bearing D66 or A23 as an ascitic form were given i.p. injections of Nocardia rubra cell wall skeleton (N-CWS). N-CWS significantly prolonged the survival period of mice bearing D66, whereas it exhibited no apparent antitumor effect on mice bearing A23. The increase in the cell number of D66 in the peritoneal cavity was significantly retarded, compared with that of A23. In contrast, the number of peritoneal macrophages increased more in D66-bearing mice than in A23-bearing mice. The increase in the peritoneal macrophage number was further augmented by an i.p. injection of N-CWS. Peritoneal macrophages of D66-bearing mice exhibited apparent tumoricidal activity against MM48 tumor cells in the presence of lipopolysaccharide, and the cytotoxicity was significantly augmented by i.p. injection of N-CWS. On the other hand, the responsiveness of peritoneal macrophages to lipopolysaccharide was found to be poor in A23-bearing mice and the tumoricidal activity was only weakly augmented by N-CWS. These results strongly suggest that M-CSF plays an important role not only in the maturation of macrophage progenitors but also in the induction and the accumulation of activated macrophages.
Cancer Immunol Immunother 1989
PMID:Induction of tumoricidal macrophages from bone marrow cells of normal mice or mice bearing a colony-stimulating-factor-producing tumor. 264 51

Nylon-wool-eluted lymphocytes, isolated from a site of tumor rejection in Balb/c mice expressing concomitant tumor immunity, were examined for their ability to inhibit the growth of the EMT6 tumor. Tumor growth inhibition was monitored after co-inoculation of lymphocytes and tumor cells into naive mice in a Winn-type adoptive-transfer assay. A pre-implanted gelatin sponge was employed to capture the tumor-infiltrating lymphocytes. Mice harboring primary tumors were implanted 8 days later with gelatin sponges. The pre-implanted sponges were then inoculated with a secondary tumor challenge 2 days after implantation of the sponge (i.e. 10 days after primary tumor challenge). On day 17 (7 days after secondary tumor challenge), the immune sponges were retrieved, digested in collagenase and the T lymphocytes were isolated using a nylon-wool column. Blank sponges (lacking tumor cells), obtained from primary-tumor-bearing or non-tumor-bearing animals, were included for comparison. The data showed that T lymphocytes isolated from immune sponges inhibited tumor growth while T lymphocytes recovered from blank sponges did not. At an effector:target (E:T) ratio of 10:1 the lymphocytes from the immune sponges were able to prevent totally the growth of tumors in all cases (100% inhibition). This ability was reduced (60% inhibition) at an E:T ratio of 1:1. Comparison of the antitumor activities of the immune-sponge-derived cells with those from the spleen of the same animal revealed the superiority of the former. Depletion of immune-sponge-derived cells with anti-Thy1.2, anti-Lyt2.2 or anti-L3T4 and complement resulted in a marked decrease in tumor-inhibitory activity. These results indicate that T lymphocytes, expressing Thy1.2, Lyt2.2 or L3T4 antigens, are involved in conferring protection to Balb/c mice against the EMT6 tumor.
Cancer Immunol Immunother 1989
PMID:Implantation of a gelatin-sponge as a model for effector recruitment. Tumor growth inhibition by T-lymphocytes recovered from a site of tumor rejection. 278 57

Nonparenchymal liver cells from untreated C3HeB/FeJ mice, when incubated in medium containing-10% fetal bovine serum or portal serum, produced significant amounts of interferon alpha/beta (IFN alpha/beta). In contrast, other cell populations (spleen, mononuclear blood cells and peritoneal cells) from C3HeB/FeJ mice or nonparenchymal liver cells from other strains of mice (C3H/HeJ, germ-free C3H/HeN and C57Bl/6J) produced little or no detectable IFN in fetal bovine serum under the same culture conditions. The cells in the nonparenchymal liver cell population responsible for IFN alpha/beta production were adherent, phagocytic, silica-sensitive, carbonyl-iron-sensitive, and Thy1.2-, presumably Kupffer cells or resident liver macrophages. IFN alpha/beta production by cultured Kupffer cells was not observed if medium containing fetal bovine serum or portal serum was treated with polymyxin B or if Kupffer cells were cultured in serum-free medium. This suggested that small amounts of endotoxin in fetal bovine or portal serum stimulated Kupffer cells to produce IFN alpha/beta. Possibly, Kupffer cells are in a different state of activation/maturation than peritoneal and splenic macrophages since the sensitivity of resident Kupffer cells from C3HeB/FeJ mice to the stimulatory effects of endotoxin. The endogenous production of IFN alpha/beta by Kupffer cells from C3HeB/FeJ mice can augment liver-associated natural killer (NK) activity against YAC-1 cells (4h) and induce liver-associated cytotoxic activity, not restricted by the major histocompatibility complex, against NK resistant P815 mastocytoma cells (18 h).
Cancer Immunol Immunother 1989
PMID:Endogeneous interferon alpha/beta produced by murine Kupffer cells augments liver-associated natural killing activity. 291 63

Cells required for the in vitro generation of syngeneic cytotoxic T-lymphocytes (CTL) against the P815 mastocytoma in the DBA/2 mouse strain were investigated. For both immune and tumor-bearing host spleen cells, CTL effector cells were eliminated by treatment with anti-Thy1.2, anti-Lyt1.1, or anti-Lyt2.1 and C', but were resistant to anti-L3T4 (GK1.5). Thus, CTL effectors (and their precursors) were Lyt1+2+, L3T4-. However, P815-specific CTL could not be generated in the absence of L3T4+ cells, whose function could be replaced with exogenous interleukin-2 (IL-2). When monoclonal antibodies against L3T4 were added to mixed leukocyte tumor cultures, CTL generation was markedly inhibited. Depletion of accessory cells also led to a marked reduction in CTL generation, which could be restored to control levels by adding adherent cells from normal spleens or with exogenous IL-2, but not with IL-1. Thus, accessory cells are apparently required to present the tumor antigens of this Ia-negative tumor to T-helper cells.
Cancer Res 1988 Mar 15
PMID:Phenotype of syngeneic tumor-specific cytotoxic T-lymphocytes and requirements for their in vitro generation from tumor-bearing host and immune spleens. 296 66

A non-neoplastic T cell population associated with a murine monoclonal B cell malignancy, CH44, was analyzed. Immunofluorescence on cell suspensions and immunoperoxidase staining on tissue sections using monoclonal antibodies to the antigens Thy1.2, Ly-1, L3T4, and Lyt-2 confirmed the presence of both TH (Ly-1/L3T4+, Lyt-2-) and Tc/s (Ly-1/L3T4-, Lyt-2+) T cell subpopulations. The non-neoplastic T cells were present in both a 0.6 and 2.1 g CH44-bearing spleen. T cells, not normally in liver in significant numbers, were found in liver tissue when the CH44 tumor cells were present. These data implied an active proliferation of the T cell populations within tissues containing the malignant B cells. Supernatant from an in-vitro-adapted cell line of CH44 (CH44.LX) was tested for its ability to induce proliferation of normal murine splenocytes and thymocytes. As assayed by tritiated thymidine incorporation, both spleen and thymus cells proliferated in the presence of CH44.LX supernatant. Although supernatant from two of nine other B cell lines was able to stimulate the proliferation of spleen cells, only CH44.LX could induce proliferation of thymus cells. Supernatant from the seven other B cell lines and three hybridomas had no measurable effect on either splenocytes or thymocytes in this assay. It is hypothesized that the presence of a non-neoplastic proliferating T cell population associated with a neoplastic B cell lymphoma during in vivo passaging of the tumor is the result of effects derived from a secreted product of the malignant B cells. Whether the T cells have any effect on the growth of the malignant B cells is not known.
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PMID:Analysis of a murine B cell lymphoma, CH44, with an associated non-neoplastic T cell population. I. Proliferation of normal T lymphocytes is induced by a secreted product of the malignant B cells. 297 41

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.
Int J Cancer 1986 May 15
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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