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C C Ting

Publications and source records attributed to C C Ting.

At least 19 recordsLinked to original sources
PubMed1979

Suppression of T cell-mediated immunity by tumor cells: immunogenicity versus immunosuppression and preliminary characterization of the suppressive factors.

In studying the immunogenicity of spleen cells and tumor cells in the generation, of cytotoxic T lymphocyte (CTL) in the allogeneic mixed lymphocyte culture (MLC) or mixed lymphocyte tumor cell culture (MLTC) reactions, we have found that the tumor cells not only appear to be poorly immunogenic, but are also immunosuppressive. This was shown by the ability of the tumor cells or their cell-free extracts to suppress standard MLC reactions. This suppression was acting mainly at the induction phase of the cytotoxic response. It could not interfere with the killing activity of the fully generated CTLs. In a Friend virus-induced leukemia FBL-3 system, at least two major components could be attributed to the cause of immunosuppression; one was of viral origin and the other was of non-viral origin. The viral component was sensitive to UV-irradiation and could be pelleted after ultracentrifugation at 100,000 g. The non-viral component was UV-resistant and was retained in the supernatant fraction after ultracentrifugation. Friend virus and 12 commonly found murine viruses have been excluded as the possible candidates causing the immunosuppression. The immunosuppressive viruses are very likely of endogenous origin and are defective in replication as shown by electromicroscopy, and by the virus focus-inducing and reverse transcriptase assays. These findings indicate that probably all tumor cells possess the immunosuppressive factor(s) which may account for their apparent lack of immunogenicity and the lack of proper immune responses in the tumor-bearing hosts.

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PubMed1979

Studies of the mechanisms for the induction of in vivo tumor immunity. IV. Enhancement of the in vitro generation of secondary cell-mediated cytotoxic response by normal peritoneal macrophages and their culture supernatants.

The effect of macrophages on the induction of the cell-mediated cytotoxicity against a leukemia in a syngeneic system was investigated. The addition of exogenous peritoneal cells from normal C57BL/6 MIce enhanced the in vitro secondary cell-mediated cytotoxic response of both spleen and lymph node cells as responding cells against syngeneic FBL-3 leukemia. Peritoneal phagocytic macrophages seemed to be responsible for the enhancement. No inhibitory effect was demonstrated by the addition of peritoneal macrophages at a concentration as high as 20%, whereas the primary cytotoxic allograft response was significantly suppressed. In the present studies, there was no absolute restriction of macrophage-T cell interaction by an H-2 barrier. Supernatants of peritoneal macrophage cultures also enhanced this cell-mediated cytotoxic response. There was no difference between the effects of syngeneic or allogeneic peritoneal macrophage culture supernatants.

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PubMed1978

Expression of fetal antigens in fetal and adult cells during long-term culture.

Expression of fetal antigens in early and late passages of tissue culture cells derived from C3H/HeN and C57BL/KaLw mouse fetal cells and from lung tissue of young C57BL/6N mice was investigated by the isotopic antiglobulin technique. The late passage lines of fetal cells had undergone "spontaneous" neoplastic transformation in culture. The antisera were produced by syngeneic immunization with 5000 R x-irradiated tissues from C3H/HeN and C57BL/6N fetuses of 1 to 2 weeks gestation. Fetal antigens were found to be retained even after 5 years in cell lines derived from fetal tissues. In these lines no consistent change in fetal antigen expression could be correlated with neoplastic transformation. In contrast, the early passages of adult cells did not have detectable amounts of fetal antigens. However, fetal antigen(s) was demonstrated in cells of the late passages, and cells of both lines grew as sarcomas when next assayed 55 days later. In addition, fetal antigens were also present in established tumor lines in culture.

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PubMed1978

Studies of the mechanisms for the induction of in vivo tumor immunity. II. Distribution and homing of cytotoxic effector and precursor cells.

Cytotoxic T (thymus)-lymphocytes (CTL) with specific cytotoxicity against the leukemia-associated antigens of FBL-3, a syngeneic Friend virus-induced leukemia in C57BL/6 mice, could be adoptively transferred to sublethally X-irradiated (350 R) syngeneic hosts and could be induced by adoptive transfer of either normal or presensitized lymphocytes obtained from immunocompetent hosts. The CTL and their precursor cells were systemically distributed in peripheral lymph nodes and spleen, although they had the tendency of homing to the lymphoid tissue of the same origin. Direct cytotoxicity was obtained with the lymphocytes from these lymphoid tissues, and cells obtained from these lymphoid tissues could produce secondary cytotoxic responses by the mixed lymphocyte tumor cell culture reactions 40--60 days after adoptive transfer. In addition, lymph node and spleen cells had a synergistic effect on the induction of cytotoxicity. These findings indicated that tumor immunity was widely distributed and that various populations of lymphocytes were involved in the generation of efficient cell-mediated cytotoxic responses.

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PubMed1977

Solubilized TSTA and the major viral structural proteins, gp70 and p30, in the immune response to murine leukemias induced by Friend and Rauscher virus.

Antigens present in gp70 and p30 purified from Rauscher virus, were tested for immunogenicity in various assays measuring the anti-tumor immune response against lymphocytic leukemias of Friend (FBL-3) or Rauscher (RBL-5) virus origin. p30 had no effect on in vitro cytotoxicity against tumor cell targets mediated by either an anti RBL-5 serum or lymphocytes from animals immunized with FBL-3 cells. gp70 had had no effect on serum-mediated cytotoxicity but used at high concentrations it inhibited cell-mediated cytotoxicity. When used to immunize mice directly against subsequent challenge with the RBL-5 and FBL-3 leukemias, p30 had no discernible effect, while gp70 afforded partial protection against RBL-5 but only at high concentrations. Cell-free preparations of tumor membranes containing negligible amounts of gp70 were antigenically superior to gp70 in both the in vitro and in vivo assays. It is concluded that antigens on these purified proteins that are also expressed on tumor cells are not major targets of the anti-tumor immune response in this system.

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PubMed1977

Host control of tumor growth.

A humoral factor (molecular weight less than 60,000) that was present in the ascitic fluid of mice bearing intraperitoneal tumors and in pleural effusions from human cancer patients was found to promote the growth of a murine tumor and to suppress cell-mediated tumor immunity. However, the hosts that had recovered from the immunosuppressive state produced a serum factor that could neutralize the immunosuppressive effect.

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PubMed1977

Comparison of three isotopic assays of cell-mediated cytotoxicity against mouse tumor cells. I. Basic parameters: baseline controls, target cells, and methods of calculation.

We compared three ddifferent isotopic assays of cell-mediated cytotoxicity under identical test conditions: 51Cr, 125iododeoxyuridine, and [3H]proline release assays. We made these comparisons both in a syngeneic mouse tumor system and an allogeneic system. It was found that several parameters could affect considerably the results obtained with these tests, such as: baseline controls, preparation of target cells, and methods of calculation. In comparison of three different baseline controls, the normal control gave the most consistent results, whereas the other two controls (autologous and medium controls) gave varying results depending upon the condition of the target cells. For use as target cells, established tissue culture cells were usually superior because of a much lower spontaneous release of the isotope, when compared to fresh ascites tumor cells or short-term tissue culture cells. The advantage of established culture cells was particularly noted in isotopic assays with prolonged incubation (20-40 hr). In addition, the methods used for calculation were also shown to affect the apparent outcome of the results.

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PubMed1977

Comparison of three isotopic assays of cell-mediated cytotoxicity against mouse tumor cells. II. Sensitivity and specificity of the assays and characteristics of effector and sensitizing cells.

Three assays of cell-mediated cytotoxicity in mice, involving release of either 51Cr (CRA), 125iododeoxyuridine (IRA), or [3H]proline (PRA), were compared under identical test conditions. Experiments were performed with effector cells from mice immunized with FBL-3 tumor cells, a syngeneic Friend virus-induced leukemia, or with allogeneic normal spleen cells. With established tissue culture cells as targets, similar results were obtained in all three assays. The cytotoxicity produced by cells from in vivo-immunized mice and the induction of cytotoxicity in vitro were T-cell-dependent. When short-term culture target cells were used, the IRA gave a more selective pattern of cytotoxicity than did the other two assays. However, when remaining target cells at the end of the assay were treated with trypsin, higher levels of 125iododeoxyuridine (125IUDR) release were seen, and the results were then comparable to those in the CRA and PRA. These results indicated that 125IUDR, a nuclear label, could only be released after lysis of cells. In contrast, 51Cr or [3H]proline, which are cytoplasmic labels, could also be released from damaged but unlysed cells. These fundamental differences could give different results in these assays, which could determine their correlation with in vivo transplantation immunity.

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PubMed1977

Studies of H-2 restriction in cell-mediated cytotoxicity and transplantation immunity to Leukemia-associated antigens.

H-2 dependency of T cell-mediated cytotoxicity and transplantation immunity to leukemia-associated antigens has been investigated. Through the use of a 20-hr 125IUdR release assay, it was found that the induction of T cell-mediated cytotoxicity against Friend virus-induced leukemias of different H-2 haplotype orgins could be produced by immunization with both syngeneic and allogeneic tumor cells; the effector cells that were generated by syngeneic immunization could also provide effective killing of allogeneic tumor cells, although the killing of allogeneic targets might require a longer incubation time (20 to 40 hr). Furthermore, in vivo transplantation immunity against Friend virus-induced leukemias also was induced by immunization with both syngeneic and allogeneic tumors and syngeneic immunization could induce specific protection against the challenge with a-logeneic tumor in x-irradiated hosts. These findings clearly indicate that, both at the sensitizing phase and effector phase of the immune response, there is no strict H-2 dependency for T cell-mediated cytotoxicity or in in vivo transplantation imunity to leukemia-associated antigens.

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PubMed1976

Detection of anti-tumor antibody in virally induced tumors and its relationship to tumor growth.

The humoral antibody response to virally induced tumors insyngeneic hosts has been studied. The tumors include an SV40 tumor SVT2, the Friend virus-induced leukemias FBL-3 and FLC; and Moloney sarcoma virus-induced tumors. It was found that antitumor antibodies could be detected by the isotopic antiglobulin technique in these tumor systems at a relatively early stage of tumor growth. The kinetics of the antibody response in relation to the status of tumor growth varied between different tumors. In geneumor growth than in the regressors of tumor-free hosts. Reinoculation of tumor cells or recurrence of tumor growth produced elevation of antibody levels (secondary response). The specificity of the antibody reactions also varied in different tumor systems: some antibodies were truly tumor-specific and thus might produce a biological effect on in vivo tumor immunity, whereas others were not. These studies indicated that a sensitive antibody assay could be used for early detection of tumor growth. However, its usefulness in evaluation of the status of tumor growth should be carefully studied in each tumor system.

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PubMed1976

Cell-mediated immunity to Friend virus-induced leukemia. II. Characteristics of primary cell-mediated cytotoxic response.

The primary cell-mediated cytotoxic response to a Friend virus-induced leukemia, FBL-3, in C57BL/6 mice was measured by the 125IUdR release assay. Intraperitoneal (i.p.) inoculation of 1 x 10(1) FBL-3 cells produced progressive tumor growth (progressors); subcutaneous (s.c.) inoculation of as many as 5 x 10(6) FBL-3 cells produced only transient tumor growth (regressors), and these mice would subsequently resist i.p. challenge of FBL-3 cells at 3 days after s.c. inoculation. The kinetics of the primary cell-mediated cytotoxic response of regressors was biphasic. Significant cytotoxicity could be detected at 3 to 5 days after s.c. inoculation of 5 x 10(6) FBL-3 cells peaked at days 10 to 14, declined to a very low level or became undetectable around days 20 to 30; then the reactivity reappeared and persisted at least up to 60 days. In progressors, the kinetics of the cell-mediated cytotoxic response was similar to the regressors, but the reactivity was much lower. The cytotoxic response was found to be T cell dependent, during both the first peak (days 10 to 14) and the second peak (days 40 to 60). In adoptive transfer experiments, lymphocytes from regressors gave 90% protection against i.p. challenge of FBL-3; lymphocytes from progressors only gave 40% protection.

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PubMed1976

Cell-mediated immunity to Friend virus-induced leukemia. III. Characteristics of secondary cell-mediated cytotoxic response.

By employing the 125IUdR release cytotoxicity assay, we have been able to measure the primary and secondary cell-mediated cytotoxic response of C57BL/6 mice to FBL-3 cells, a syngeneic Friend virus-induced leukemia. It was found that the secondary cell-mediated cytotoxic response occurred more rapidly after challenge (within 3 days) than the primary response, and the levels of reactivity were considerably higher. As in the primary response, the secondary cytotoxic reactivity of spleen cells was T cell dependent, being eliminated by pretreatment with anti-theta antibody plus complement. However, the secondary reactivity of pertioneal exudate (PE) cells was not entirely T-cell dependent. The specificity of the secondary cytotoxic response was analyzed by primary or secondary immunization with various tumor cells and by testing of cytotoxic lymphocytes against a variety of target cells. When spleen cells were used for testing, only tumor cells induced by Friend, Moloney, or Rauscher (FMR) leukemia viruses could produce secondary cell-mediated cytotoxic responses against FBL-3 cells. This correlated well with the specificity observed in the in vivo tumor transplantation protection studies. Similarly, spleen cells immune to FBL-3 had appreciable cytotoxicity against tumor cells induced by FMR viruses. The FBL-3 immune mice also gave significant protection against the challenge of FMR leukemias. When PE cells were used for testing, they gave higher levels of cytotoxicity against tumor cells induced by FMR viruses, but also gave less, but appreciable, cytotoxicity against non-FMR tumors. The latter reactivity might be related to the antigens induced by the murine endogenous type C viruses.

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