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C C Ting

Publications and source records attributed to C C Ting.

At least 55 records · Page 3Linked to original sources
PubMed1982

Tumor cell-triggered macrophage-mediated suppression of the T-cell cytotoxic response to tumor-associated antigens. I. Characterization of the cell components for induction of suppression.

A tumor cell-triggered macrophage-mediated suppressor mechanism was demonstrated. It suppressed the induction of specific tumor immunity in the syngeneic, primary mixed lymphocyte tumor cell culture reactions. Preexposure of splenic adherent cells (SAC) to syngeneic FBL-3 tumor cells induced complete suppression of the generation of cytotoxic T-cells. The SAC responsible for inducing suppression were consistent with being macrophages. They were resistant to the treatment of anti-Thy-1.2 antibody plus complement and were relatively radioresistant (at least less than or equal to 750 R X-radiation). Adherent cells obtained from lymph nodes or thymuses acted in the same way as SAC. However, preexposure of peritoneal adherent cells to tumor cells failed to induce suppression. In contrast, the simultaneous presence of peritoneal adherent cells with SAC upon exposure to tumor cells prevented the induction of suppression. These peritoneal cells were also consistent with being macrophages. These results confirmed our previous observations obtained with experiments performed in the allogeneic system. An immunoregulatory circuit existed between two subsets of macrophages that were derived from the population of cells in the peritoneal cavity and from spleen, lymph nodes, or thymus. In the presence of tumor cells, these macrophages produced both positive regulation and negative regulation of the T-cell-mediated cytotoxic response against syngeneic tumor cells. The tumor cells may have utilized the host's own immune network to activate the suppressor mechanisms, thus successfully evading the host's immune surveillance.

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PubMed1982

Tumor cell-triggered macrophage-mediated suppression of the T-cell cytotoxic response to tumor-associated antigens. II. Mechanisms for induction of suppression.

The mechanisms were investigated for the tumor cell-triggered macrophage-induced suppression of T-cell-mediated tumor immunity. Interaction between tumor cells and macrophages triggered the production of prostaglandin(s) (PG) that initiated the suppressor events. In our experiments, PGE1 or PGE2 suppressed the generation of cytotoxic T-lymphocytes in the syngeneic mixed lymphocyte tumor cell cultures. Indomethacin, a PG synthetase inhibitor, blocked the induction of the macrophage-mediated suppression, which suggested that suppression was caused by endogenous PG. This suppression might be further mediated by the generation of suppressor T-cells. Significant reduction in the levels of macrophage-induced suppression was seen in hosts receiving cyclophosphamide treatment, which could eliminate the precursors of suppressor T-cells. These findings indicated that tumor cells may trigger a chain of reactions, through the generation of suppressor factors or suppressor cells, to subvert the host's immune surveillance.

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PubMed1980

Evaluation of the immunocompetence of macrophages and the generation of T-cell-mediated cytotoxic response against allogeneic tumor cells in tumor bearers.

The present study has examined the competence of peritoneal cells (PC) I of tumor bearers to reverse the immunosuppressive effect of tumor cells, and the ability of the tumor bearers to generate a T-cell-mediated cytotoxic response against allogeneic spleen cells or allogeneic tumor cells. It was found that PC from tumor bearers possess a greater ability to reverse the tumor cell immunosuppression in normal mice. In contrast to normal hosts, the cytotoxic responses of the tumor bearers against allogeneic tumor cells cannot be restored by PC from normal mice or from tumor bearers. The ineffective cytotoxic response in tumor bearers was not due to deficient T responders or T helpers. Rather, it was due to the presence of suppressor cells which were adherent, radioresistant and resistant to anti-Thy-1.2 antibody lysis, and thus were likely to be macrophages. The suppressor macrophages were present only in the spleen and were absent from the peritoneal cavity of the tumor bearers. Their suppressive effect can only be exerted in the presence of tumor cells. These results demonstrate the dichotomy of macrophage function, peritoneal macrophages from the tumor bearers showing increased activity of augmentation of T-cell-response whereas the splenic macrophages cause suppression of the T-cell-response.

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PubMed1980

Switching on the macrophage-mediated suppressor mechanism by tumor cells to evade host immune surveillance.

The present study demonstrates a unique mechanism for tumor cell-induced immunosuppression. In the presence of a nonsuppressive dose of tumor cells, generation of cytotoxic T cells in the mixed lymphocyte culture (MLC) is completely suppressed by adding exogenous (peritoneal) macrophages (PM phi) after the initiation of the MLC. This indicates that tumor cells can switch on a suppressor mechanism through host macrophages. It has further been determined that suppression can be induced only if resident (splenic) macrophages (SM phi) are exposed to tumor cells prior to addition of PM phi. If SM phi and PM phi are simultaneously present with the tumor cells, induction of suppression is completely precluded. These findings indicate that switching on of the suppressor mechanism by tumor cells has a critical requirement for the collaboration of two populations of macrophages, SM phi and PM phi, and their presence in a specific sequence (SM phi preceding PM phi). This may represent one of the mechanisms by which tumor cells evade host immune surveillance.

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PubMed1980

Increased susceptibility to tumor cell immunosuppressive effect in tumor-bearing mice.

Compared to normal hosts, tumor-bearing BALB/c mice were more susceptible to the immunosuppressive effect of tumor cells. At least a tenfold increase was found in the susceptibility mediated by a population of radioresistant spleen adherent cells (AC). The experiments were performed by the study of the suppressive effect of tumor cells on the generation of cytotoxic T-cells in allogeneic mixed lymphocyte culture reactions and allogeneic mixed lymphocyte tumor cell culture reactions. Fewer tumor cells were needed to suppress the T-cell-mediated cytotoxic responses of tumor bearers compared to normal hosts. A normal spleen population could be made to react like the tumor-bearing host by first depletion of its normal macrophages and then reconstitution with spleen AC from tumor bearers. Conversely, reconstitution of the macrophage-depleted tumor bearer's spleen with normal spleen AC made the tumor bearer react like the normal host. Furthermore, tumor cells were needed to trigger the spleen AC of the tumor bearer to fully exert their effect.

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PubMed1980

Characterization of the responding populations for the generation of proliferative response to syngeneic Meth A tumor in BALB/c mice: requirement of T and B cell collaboration.

High levels of primary proliferative response to a chemically induced sarcoma Meth A can be induced in syngeneic BALB/c spleen cells. Testing at the peak of proliferative response (2 days after sensitization in the mixed lymphocyte tumor cell culture), we found the responders to be resistant to anti-Thy 1.2 antibody lysis but susceptible to anti-Ia antibody lysis. When responders were subjected to various treatments before sensitization, it was found that removal of macrophages had no effect on the generation of proliferative response; high levels of proliferative response could be induced in enriched B cell preparations and in spleen cells from nude mice, but there was only a negligible amount of response in enriched T cell preparations. These findings indicate that the responders are primarily B lymphocytes. However, it was also found that the enriched B cell preparations usually gave only 50 to 75% of the response of whole spleen cells, whereas these B cells gave a 2- to 3-fold increase in the response to a B cell mitogen, LPS; this result indicate that collaboration from other types of lymphocytes was required for the generation of an optimal proliferative response to Meth A. Addition of 10% of T cells indeed produced a helper effect on this B cell response, and the maximal helper effect was seen for a mixture containing equal parts of T cells and B cells or for a slight T cell excess. These results indicate that the proliferative response to a syngeneic Meth A tumor is a macrophage-independent T-dependent B cell response.

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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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