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S Shu

Publications and source records attributed to S Shu.

At least 109 records · Page 6Linked to original sources
PubMed1989

Development of antitumor reactivity in regional draining lymph nodes from tumor-immunized and tumor-bearing murine hosts.

With use of the weakly immunogenic MCA 105 tumor of the C57BL/6 mouse, the antitumor reactivity of lymphoid cells derived from the regional draining lymph nodes (RLN) of tumor-immunized and tumor-bearing mice was examined. Mice were immunized with an inoculation of viable tumor admixed with Corynebacterium parvum. Excision of tumor immunization sites within 4 days abrogated the development of systemic immunity to reject a tumor challenge. However, excision of the immunization site on day 6 did not interfere with the development of systemic antitumor immunity. In subsequent experiments, tumor immunization sites were excised on day 6 in all mice and the RLN either left intact or excised on day 6 or day 14. The development of systemic tumor immunity was severely impaired if RLN were excised on day 6, indicating the pivotal role of the RLN. Excision of the RLN on day 14 had no impact on the development of systemic immunity, thus indicating that the requirement for the RLN was time dependent. In mice bearing progressively growing tumors, lymphoid cells derived from RLN were examined for therapeutic efficacy in adoptive immunotherapy experiments. Although fresh RLN cells harvested 6 and 14 days after tumor inoculation did not demonstrate inherent therapeutic efficacy, after in vitro sensitization with irradiated tumor cells and interleukin-2, these RLN cells acquired significant antitumor activity in adoptive immunotherapy experiments. These data indicate that RLN are essential in the development of tumor immunity and may be used as a source of therapeutic effector cells for adoptive immunotherapy.

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PubMed1988

Adoptive immunotherapy of microscopic and advanced visceral metastases with in vitro sensitized lymphoid cells from mice bearing progressive tumors.

Lymphocytes from mice bearing the weakly immunogenic MCA 105 sarcoma contained pre-effector cells that could be sensitized and expanded in vitro to acquire anti-tumor reactivity. The in vitro sensitization (IVS) required antigenic stimulation by tumor cells and the presence of IL-2 for cellular proliferation. Recent work has also demonstrated that IVS cells could be generated in an IL-2 concentration as low as 2 U/ml. In the present study, we have evaluated therapeutic efficacy of IVS cells generated in different concentrations of IL-2 against advanced metastases established in the lung as well as in the liver. Treatment of microscopic or grossly visible pulmonary metastases established for 3 or 10 days by systemic transfer of IVS cells resulted in significant reductions of the numbers of metastases. On a per cell basis, IVS cells generated in 2 U/ml of IL-2 exhibited at least twofold greater reactivity than cells generated in 1000 U/ml of IL-2. In survival experiments, treatment of established microscopic (day 3) and visible (day 10) pulmonary metastases with 1.5 x 10(7) and 3 x 10(7) IVS cells generated in 2 U/ml of IL-2 resulted in prolongation of survival and cure of the disease in 60 and 30% of animals, respectively. The systemic anti-tumor effect of IVS cells was further investigated in mice with hepatic metastases. Treatment of day 3 microscopic hepatic metastases revealed that as little as 1.2 X 10(7) IVS cells generated in 2 U/ml of IL-2 reduced the mean number of metastases from more than 250 in various control groups to 32. Evaluation by survival demonstrated that transfer of 1.7 x 10(7) and 3.8 x 10(7) IVS cells was capable of prolonging the survival and curing 40 and 30% of mice bearing day 3 and day 9 hepatic metastases, respectively. Again, IVS cells generated in 2 U/ml of IL-2 were more effective therapeutically than cells generated in 1000 U/ml of IL-2. In all experiments, mice were also given IL-2 to enhance the in vivo reactivity of IVS cells. However, the doses of IL-2 alone had no therapeutic benefit. Taken together, our results show that adoptive immunotherapy with IVS cells generated from tumor-bearing mice was an effective means of eliminating advanced metastases in various visceral organs.

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PubMed1988

Cellular basis of immunologic interactions in adoptive T cell therapy of established metastases from a syngeneic murine sarcoma.

The adoptive transfer of specifically sensitized T lymphocytes can effectively mediate the regression of established local and metastatic tumors. Previous experiments using the weakly immunogenic MCA 105 sarcoma indicated that cellular interactions between transferred L3T4+ helper and Lyt-2+ cytotoxic immune T cells were necessary for mediating tumor regression. In this study, the kinetics of T-T cell interactions were analyzed by in vivo depletion of T cell subsets with mAb. The anti-tumor efficacy of transferred immune cells was abrogated by in vivo administration of either L3T4 or Lyt-2 mAb on the day of cellular therapy. However, if mAb were given 3 days after the transfer of immune cells, depletion of Lyt-2+ but not L3T4+ cells abrogated anti-tumor efficacy. T cell depletion on day 6 after transfer of immune cells had no adverse effect on tumor regression, indicating the period required for T cell reactivity in vivo. Furthermore, depletion of Ia+ cells by in vivo mAb treatment abrogated the anti-tumor efficacy of immune cells. It is thus hypothesized that there are two distinct but sequential phases of in vivo T cell interactions leading to the regression of established tumors after adoptive immunotherapy. An initial "helper/inducer" phase apparently requires the interaction of L3T4+ immune cells and the tumor Ag involving Ia+ cells. The inducement of L3T4+ cell activation is to provide helper function via the secretion of IL-2. The second phase designated as an "effector phase" involves differentiation of immune Lyt-2+ cells under the influence of IL-2 secreted during the helper/inducer phase for generation of mature Lyt-2+ effector cells. To further support the hypothesis of a two-phase process we have examined the phenotype and kinetics of tumor regression mediated by effector cells generated by secondary in vitro sensitization (IVS). Although the IVS cells were generated from fresh MCA 105 immune spleen cells, their anti-tumor efficacy was mediated solely by Lyt-2+ lymphocytes. Kinetic studies revealed that the in vivo requirement of IVS Lyt-2+ effector cells to mediate tumor regression was less than 3 days, and the anti-tumor reactivity of these cells was not affected by in vivo depletion of Ia+ cells. Thus, the IVS reaction is likely representative of the in vivo counterpart of the helper/inducer phase leading to the generation of mature Lyt-2+ immune effector cells. Tumor regression after transfer of Lyt-2+ cells generated in IVS therefore required a relatively shorter period of time than that required after the transfer of fresh noncultured MCA 105 immune spleen cells.

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PubMed1987

Cellular interactions and the role of interleukin 2 in the expression and induction of immunity against a syngeneic murine sarcoma.

We have previously demonstrated that following the adoptive transfer of immune cells, the regression of established pulmonary metastases from a weakly immunogenic sarcoma, MCA 105, required the collaboration of two T cell subsets. In this study, we found that the critical role played by L3T4+ immune cells was to provide a helper function since tumor regression proceeded in the absence of L3T4+ immune cells if exogenous interleukin 2 (IL-2) was administered. To extend these observations, we analyzed the events leading to the induction and generation of L3T4+ and Lyt-2+ immune T cells after immunization of mice with viable tumor cells admixed with Corynebacterium parvum. The basic protocol involved immunization, surgical excision of the immunization site on day 7, and challenge with viable tumor cells on day 21. The ability of mice to reject tumor challenge provided a means to evaluate the occurrence of a systemic antitumor immunity. With the use of this experimental protocol, we have found that depletion of T cell subsets in vivo with either L3T4 or Lyt-2 monoclonal antibodies after active immunization abrogated the development of antitumor immunity. Mice immunized and depleted of L3T4+ but not Lyt-2+ T cells were able to reject tumor challenge if exogenous IL-2 was given for 7 days. However, the rejection of tumor challenge required 3 days of additional exogenous IL-2 administration. These results indicate that the induction of Lyt-2+ immune T cells depended on the helper function of L3T4+ T cells via the secretion of IL-2. In the absence of L3T4+ immune lymphocytes, the expression of antitumor immunity by Lyt-2+ immune cells could be facilitated by in vivo administration of exogenous IL-2. The induction of L3T4+ immune T cells, on the other hand, occurred independently of the Lyt-2+ T cell response because the transfer of spleen cells from Lyt-2+ cell-depleted, immunized animals was able to restore antitumor reactivity in L3T4+ cell-depleted, immunized mice. These results demonstrate the intricate cellular interactions leading to the induction as well as the expression of antitumor immunity.

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PubMed1987

In vitro differentiation of T-cells capable of mediating the regression of established syngeneic tumors in mice.

Previous studies have shown that successful adoptive immunotherapy of a newly induced, weakly immunogenic murine sarcoma, MCA 105, can be achieved either with fresh noncultured immune spleen cells or with immune cells after in vitro stimulation and expansion. In this study, we utilized in vivo and in vitro depletions with monoclonal antibodies (mAb) of T-cell subpopulations expressing the L3T4 or Lyt-2 antigens to investigate the phenotype of the T-cells that mediate in vivo tumor regression. The efficiency of depletion was assessed by flow microfluorometric analysis and by the ability of specifically treated spleen cell populations to generate allogeneic cytotoxic T-lymphocytes. The therapeutic efficacy of adoptively transferred fresh noncultured MCA 105 immune cells was abrogated by in vivo administration of either L3T4 or Lyt-2 mAb to mice bearing 3-day established pulmonary metastases. In vitro treatment of fresh noncultured MCA 105 immune cells with either L3T4 or Lyt-2 mAb and complement also abrogated their antitumor efficacy confirming the initial findings. However, mixing L3T4 and Lyt-2 mAb and complement-treated MCA 105 immune cells reconstituted the antitumor efficacy indicating that cellular cooperation between these two lymphoid subpopulations was essential for the regression of established tumors. Unlike fresh noncultured immune cells, the antitumor efficacy of in vitro sensitized and expanded immune cells was abrogated by in vivo treatment with Lyt-2 but not with L3T4 mAb indicating Lyt-2+ cells alone played a major role in mediating the regression of tumors. These findings provide evidence for an in vitro-induced differentiation of therapeutic T-lymphocytes. Our results thus suggest that the antitumor activities expressed by the two types of cells may represent T-cells at different stages of immunological differentiation.

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PubMed1986

The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells.

Our previous studies demonstrated that the incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (RIL 2) resulted in the generation of lymphokine-activated killer (LAK) cells capable of lysing a broad spectrum of fresh tumors in short-term chromium-release assays. Moreover, injections of LAK cells plus RIL 2 were highly effective in eliminating established 3 day metastases in the lung and liver (1-3). We have examined several parameters to define whether or not the cytolytic activity of LAK cells as measured in vitro correlated directly with the in vivo anti-tumor efficacy of adoptively transferred LAK cells. LAK cells plus RIL 2 could mediate marked reductions of established pulmonary metastases in mice rendered T cell deficient by adult thymectomy and lethal, total body irradiation followed by reconstitution with T cell-depleted bone marrow and spleen cells. Thus there was no requirement for additional T lymphocytes of host origin for successful therapy with adoptively transferred LAK cells plus RIL 2. Fresh splenocytes depleted of T cells by anti-Thy-1.2 monoclonal antibody plus complement generated LAK cells that were as highly lytic to fresh tumor in vitro and were as effective in reducing established pulmonary metastases as those generated from untreated or complement-treated splenocytes. Thus the precursor to LAK cells with anti-tumor activity in vitro and in vivo did not express the Thy-1 antigenic marker. In contrast, treatment of LAK effector cells (those generated from a 3-day incubation of fresh, normal splenocytes in RIL 2) with anti-Thy-1.2 antibody plus complement reduced or abolished their in vitro cytolytic activity. However, when combined with the systemic administration of RIL 2, these T cell-depleted, non-lytic LAK cells remained as effective in reducing the number of established pulmonary metastases upon adoptive transfer as untreated or complement-treated lytic LAK cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1986

In vitro sensitization and expansion with viable tumor cells and interleukin 2 in the generation of specific therapeutic effector cells.

We have investigated the efficacy and immunologic characteristics of immune effector cells generated from cultures containing large numbers of viable tumor cells and interleukin 2 (IL 2) in the adoptive immunotherapy of experimentally induced pulmonary metastases from the newly developed, weakly immunogenic MCA 105 sarcoma in mice. The current culture conditions allowed increases of either normal or MCA 105 immune spleen cells up to 94-fold in 15 days. The in vitro expanded normal and MCA 105 immune cells displayed nonspecific in vitro cytotoxicity against several syngeneic tumor targets. However, therapeutically effective cells could only be obtained from cultures initiated with MCA 105 immune spleen cells. Immunotherapy with expanded immune effector cells could lead to the reduction of established 3 day pulmonary metastases, prolongation of survival, and cure of tumor in the majority of animals. The generation and proliferation of therapeutic effector cells in vitro depended on the presence in cultures of specific tumor stimulator cells as well as the presence of IL 2. Although immunotherapy with either fresh noncultured or secondarily in vitro-sensitized (IVS) MCA 105 immune spleen cells was immunologically specific, the efficacy of the adoptive cellular therapy with cultured but not fresh immune cells could be improved by the administration to tumor-bearing hosts of exogenous IL 2. In addition to numerical expansion, the IVS immune cells, on a per cell basis, afforded an eightfold to 10-fold increase in therapeutic efficacy when compared with fresh noncultured MCA 105 immune cells. Our results indicate that the current culture procedure induced in vitro antigenic stimulation and expansion of tumor-specific immune effector cells that was otherwise not possible by conventional mixed lymphocyte-tumor cultures.

Animals↗
PubMed1986

Adoptive immunotherapy of a syngeneic murine leukemia with a tumor-specific cytotoxic T cell clone and recombinant human interleukin 2: correlation with clonal IL 2 receptor expression.

The successful adoptive immunotherapy of the syngeneic Friend virus-induced murine leukemia FBL-3 was mediated by a proliferative MHC-restricted, tumor-specific CTL clone in combination with recombinant human IL 2. This clone was previously shown to express the L3T4-, Lyt-1+, Lyt-2+ surface phenotype. Activation of the clone for 48 hr in vitro with irradiated tumor cells induced the expression of IL 2 receptors and markedly increased clonal proliferation in response to recombinant IL 2. Intravenous injection of 2 X 10(7) 48 hr in vitro-activated cloned cells, followed by 6 days of systemic (i.p.) administration of IL 2 resulted in the complete regression of tumors and the cure of 50% of the treated mice. IL 2 alone had no effect on tumor growth, whereas the injection of nonactivated (resting) clone plus IL 2 or activated clone without IL 2 had small but insignificant effects on tumor growth and survival. These results indicated that the in vivo effector functions of cloned T cells may be markedly enhanced by the concurrent systemic administration of recombinant IL 2 and by the induction of optimal IL 2 receptor expression on the cloned T cells at the time of cell administration.

Animals↗
PubMed1986

Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo: survival benefit and mechanisms of tumor escape in mice undergoing immunotherapy.

The studies described in this paper showed that the combination of i.v.-transferred lymphokine-activated killer (LAK) cells and i.p. injections of recombinant interleukin-2 (RIL-2) was highly effective in vivo in reducing established pulmonary metastases of natural killer cell-resistant, MCA-105 sarcoma and B16 melanoma in mice. A 3-day in vitro incubation of normal C57BL/6 splenocytes in medium containing pure RIL-2 generated LAK cells that, when combined with RIL-2, reduced the mean number of established pulmonary micrometastases of the B16 melanoma and of the MCA-105 sarcoma from 179 and 140, respectively (in groups treated with Hanks' balanced salt solution alone), to 12 (P = 0.01) and 6 (P = 0.01), respectively. This combined immunotherapy also consistently resulted in significant prolongation of survival in mice with established, 3-day or 10-day pulmonary metastases of the MCA-105 sarcoma. Mice autopsied at time of death revealed a massive involvement of tumor in the lungs and liver in the group receiving Hanks' balanced salt solution alone compared to a small number of residual large lung or liver metastases in the group receiving LAK cells plus RIL-2. Experiments were designed to test whether variants existed in the original tumor cell inoculum that were resistant to killing by LAK cells and thus could account for the metastases that "escaped" the combined immunotherapy of LAK cells plus RIL-2 in vivo. Metastases of the MCA-105 sarcoma that escaped the combined therapy of LAK cells plus RIL-2 were dissected from the organs of mice upon autopsy and directly tested for susceptibility in vitro to lysis by LAK cells in 4-h and 18-h 51Cr release assays. Target cells derived from the metastases were lysed to an equivalent extent as those prepared from a fresh MCA-105 sarcoma that was growing s.c. In addition, successful reduction of pulmonary metastases established by the i.v. infusion of MCA-105 sarcoma cells obtained from metastases that escaped a prior round of therapy with LAK cells and RIL-2 could be achieved in vivo by the combined immunotherapy as well as by high doses of RIL-2 alone. Culture adapted, natural killer cell-resistant B16 melanoma cells surviving two successive treatments with LAK cells in vitro remained as susceptible to LAK cell lysis as untreated B16 melanoma cells in 18-h 51Cr release assays.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1985

Adoptive immunotherapy of a newly induced sarcoma: immunologic characteristics of effector cells.

A newly induced syngeneic transplantable sarcoma, MCA 105, was used for studies of the biologic characteristics of fresh noncultured and secondarily in vitro sensitized (IVS) cells with antitumor reactivity. Fresh spleen cells harvested from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum exhibited no detectable cytotoxic activity to MCA 105 tumor targets in a 4-hr chromium-release assay, and adoptive transfer of these cells mediated the specific regression of established MCA 105 tumors. Phenotypic analysis of fresh, noncultured immune cells revealed that the therapeutically effective cells expressed both the Lyt-1 and the Lyt-2 T cell differentiation antigens. The therapeutic efficacy of fresh noncultured immune cells was not augmented by the concomitant administration of exogeneous interleukin 2 (IL 2). Secondary IVS of fresh immune cells with irradiated MCA 105 tumor stimulator cells resulted in the generation of tumor-specific cytotoxic effector cells. The generation of cytotoxic effector cells required Lyt-1+, 2+ cytotoxic precursor cells. Effective adoptive immunotherapy with these IVS immune cells, unlike fresh noncultured immune cells, depended on the concomitant administration of IL 2. Furthermore, the generation of therapeutically effective cells did not require the specific stimulation by MCA 105 tumor cells, because cultures of MCA 105 immune spleen cells with FBL-3 lymphoma cells in vitro also contained in vivo functional immune effector cells. These cells, however, possessed no detectable MCA 105 cytotoxic activity in vitro. Although this observation suggests that a noncytotoxic cell population is sufficient to initiate tumor regression in vivo, it does not exclude the possibility that cytolytic cells are generated in vivo after adoptive transfer of these cells. As a whole, our results indicate that secondary IVS functional immune effector cells are characteristically distinct from freshly harvested immune cells.

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PubMed1985

Eradication of a disseminated syngeneic mouse lymphoma by systemic adoptive transfer of immune lymphocytes and its dependence upon a host component(s).

We have studied the in vivo effects of carrageenan and trypan blue on the adoptive immunotherapy of an established local and disseminated syngeneic mouse FBL-3 lymphoma. Mice receiving 500 rads total-body irradiation before injection of FBL-3 tumor into the footpad were treated 4 to 5 days later when a palpable local tumor and disseminated metastases were present. Injection of in vivo immune lymphocytes i.v. caused complete regression of footpad tumor and cured 96% of all mice (greater than 60 days mean survival; p less than 0.0005). Carrageenan or trypan blue treatment of the tumor-bearing host abrogated the therapeutic effect of adoptively transferred cells. Cure rates were significantly reduced to 27% (p less than 0.004) and 0% (p less than 0.0001) and mean survival times to 40.2 days (p less than 0.0005) and 15.2 (p less than 0.005) days for mice treated with carrageenan and trypan blue, respectively, in addition to immune cells. In vivo treatment of the immune spleen cell donors with carrageenan or trypan blue had no significant effect on the ability of those splenocytes to mediate cure when adoptively transferred into tumor-bearing hosts, indicating that the inhibitory activity of these agents cannot be attributed to direct toxicity to immune lymphoid cells. These results demonstrate that a recipient component(s), possibly macrophages, sensitive to carrageenan and to trypan blue but relatively resistant to radiation (500 rads), plays a vital role in the cure of tumor-bearing mice that receive the adoptive transfer of immune splenocytes.

Animals↗
PubMed1985

The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo.

We showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after the i.v. injection of syngeneic tumor cells in C57BL/6 mice. In this report, we analyzed the factors required for successful therapy. Titration analysis in vivo revealed an inverse relationship between the number of pulmonary metastases remaining after treatment and both the number of LAK cells and the amount of RIL 2 administered. Fresh or unstimulated splenocytes had no anti-tumor effect; a 2- to 3-day incubation of splenocytes in RIL 2 was required. LAK cells generated from allogeneic DBA (H-2d) splenocytes were as effective in vivo as syngeneic, C57BL/6 (H-2b) LAK cells. The anti-metastatic capacity of LAK cells was significantly reduced or eliminated when irradiated with 3000 rad before adoptive transfer. The combined therapy of LAK cells plus RIL 2 was shown to be highly effective in mice immunosuppressed by 500 rad total body irradiation and in treating macrometastases established in the lung 10 days after the i.v. injection of sarcoma cells. Further, reduction of both micrometastases and macrometastases could also be achieved by RIL 2 alone when administered at higher levels than were required with LAK cells. The value of LAK cell transfer and of IL 2 administration for the treatment of tumors established at other sites is currently under investigation.

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PubMed1984

Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2.

The activation of human peripheral blood leukocytes or murine splenocytes with interleukin-2 (IL-2) generated cells that were lytic in vitro for a variety of fresh tumor cells. The adoptive transfer of such lymphokine-activated killer (LAK) cells to mice with established pulmonary sarcoma metastases was highly effective in reducing the number (and size) of these tumor nodules when combined with repeated injections of recombinant IL-2. These findings provide a rationale for clinical trials of the infusion of human LAK cells generated with recombinant IL-2 as well as Phase I trials of the infusion of recombinant IL-2 systemically into humans.

Animals↗
PubMed1984

[Nutritional management of patients with cirrhosis after hepatectomy].

Nutritional management for the patients with cirrhosis after hepatectomy was studied. Based on the experimental results, 1-1.5g/kg/day of branched chain amino acid (BCAA) enriched solution with 30 kcal/kg/day of glucone was given to the cirrhotic patients after hepatectomy for 10-14 days. Sodium and total fluid volume were strictly restricted. Elemental diet for liver failure (ED-H) was started to give within 7 days after surgery for 6-21 days. High relationships were observed between preoperative nutritional status such as prealbumin and retinol binding protein (RBP) and incidence of postoperative complications, suggesting that postoperative nutritional supply was very important. Changes of albumin, hepaplastin test and prothrombin time were rather good and the BCAA to aromatic amino acids molar ratio was maintained high when nutritional management was performed. Overall one and two year survival rates were 74% (20/27) and 36% (5/14), respectively. No significant difference was seen between the prognoses of the patients with and without liver dysfunction. Immediate postoperative nutritional management must be essential to get over critical stage safely and long-term nutritional supply may be necessary to get better prognosis.

Hepatectomy↗
PubMed1983

Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity.

The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guérin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, "B" animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity.

Animals↗
PubMed1983

Mechanisms of immunological eradication of a syngeneic guinea pig tumor: participation of a component(s) of recipient origin in the expression of systemic adoptive immunity.

The effects of carrageenan and trypan blue on the expression of adoptive immunity to the syngeneic guinea pig line 10 hepatoma were investigated. Adoptive immunity was assessed by observing dermal tumor growth in recipients of immune cells and by bioassays in which tumor challenge sites were transplanted into secondary hosts. Carrageenan abrogated transferred immunity in treated animals as evidenced by dermal tumor growth and by development of fatal ascites tumors in peritoneal cavities of the secondary hosts. Trypan blue, on the other hand, did not abrogate transferred immunity in treated animals. However, the i.p. bioassay revealed the presence of line 10 cells in the tumor challenge sites 10 days after adoptive transfer. In vitro and in vivo exposure of immune spleen cells to carrageenan or trypan blue had no significant effect on the subsequent adoptive transfer, indicating that the inhibitory activity of these agents cannot be attributed to direct toxicity to immune lymphoid cells. Tumor challenge sites taken from carrageenan or trypan blue-treated animals 5 days after adoptive transfer failed to grow progressively when transplanted s.c. into secondary hosts. This observation suggests the presence of immune cells at tumor challenge sites. Thus, the inhibitory effects were unlikely due to interference with recirculation of the i.v.-transferred immune cells. Adoptive immunity was not influenced in guinea pigs that received a lethal dose of irradiation (500 rads). These results demonstrate that a recipient component(s) sensitive to carrageenan and trypan blue but resistant to radiation is essential to the expression of adoptive immunity.

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