Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera were found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-189.6p env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infectious doses of the CCR5 tropic SHIVSF162p4. Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor T-cell responses, but rather with the Nab titer prior to exposure.
Recently we published a hypothesis on the immunological events occurring during tumor rejection. One of the implications of this hypothesis is that specific macrophage-arming factor (SMAF) is produced early during the initiation of the immune response, whereas the "classical" cell-mediated immune response components, such as cytotoxic T lymphocytes (CTL), are produced later, that is, during the amplifier-effector phase. In this paper we establish the kinetics of the induction of (a) lymphocytes producing SMAF and (b) CTL. Groups of DBA/2 mice were injected i.p. once, twice or three times with irradiated and/or non-irradiated syngeneic SL2 tumor cells, the injections being given at intervals of 10 days. After each of these injections the production of SMAF and the expression of CTL activity were established. The results showed that in the peritoneal cavity SMAF-producing lymphocytes appeared earlier than cytotoxic lymphocytes (CTL). In addition, it was shown (a) that SMAF does not interfere with the in vitro cytotoxicity expressed by CTL and (b) that in addition to CTL memory cells, SMAF-producing memory cells were also induced after injection of syngeneic tumor cells. These data support the hypothesis that SMAF is involved in the early phase of the cellular immune response against tumors, whereas CTL are induced later.
The antitumor potency and specificity of syngeneic immune peritoneal exudate cells were tested. Groups of DBA/2 mice were immunized against syngeneic SL2 tumor cells. Then 6 days after the last immunization the antitumor potency, and the specificity of the immunization reaction was tested by injecting groups of the immunized mice with 10(3) to 5 X 10(7) DBA/2 derived L1210, L5178Y, P815 or SL2 tumor cells, and injecting immune peritoneal exudate cells into DBA/2 mice which had been injected 2 h earlier i.p. with 2 X 10(4) or 2 X 10(5) L1210, L5178Y, P815, or SL2 cells. Furthermore the tumor specific cytotoxicity in vitro of isolated immune (vs SL2) peritoneal macrophages was tested against L1210, L5178Y, P815, and SL2 cells. The "reciprocal" experiments (previous immunization against L1210, L5178Y, or P815 cells and 'challenge' with SL2) were also done. Finally, we tested the tumor-specific cytotoxicity of isolated immune peritoneal T-lymphocytes. It was shown that the rejection of tumor cells in previously immunized mice, the antitumor efficacy of the transferred immune peritoneal exudate cells and the in vitro cytotoxicity of purified immune peritoneal macrophages and lymphocytes, were tumor-specific reactions. That is only between the SL2 and L5178Y tumors were cross-reactions observed. However, this cross-reaction was not found at the level of cytotoxic T-cells. This suggests that cytotoxic T-cells and cytotoxic macrophages probably have different mechanisms of recognition of the specific tumor target cells. Treatment of macrophage monolayers, prepared from macrophages of immunized mice, with monoclonal anti-Thy-1 antibodies plus complement caused no decrease in cytotoxicity. This shows that macrophages can really express specific cytotoxicity. Tumoricidal macrophages probably obtain their tumor specificity through the activities of tumor-specific factors produced by sensitized T-cells.
DBA/2 mice were immunized i.p. against syngeneic SL2 lymphosarcoma cells. At various days after the last immunization peritoneal and spleen lymphocytes were collected. The lymphocyte suspensions were enriched for T-cells by nylon wool filtration. The peritoneal T-cells from immunized mice (a) expressed direct specific antitumor cytotoxicity in vitro, (b) induced macrophage cytotoxicity in vitro, and (c) exerted tumor neutralization measured in a Winn-type assay. Spleen T-cells from these immunized mice (a) expressed no direct specific antitumor cytotoxicity in vitro, (b) only induced moderate macrophage cytotoxicity in vitro, but (c) exerted tumor neutralization in a Winn assay. For effective tumor neutralization in vivo effector target cell ratios of 1000:1 were required. When the effector/target ratio of 1000:1 was maintained but the absolute numbers of effector and target cells were lowered from 10(6) to 10(5) lymphocytes and 10(3) to 10(2) target cells respectively, no tumor neutralization was obtained. The major effect of the sensitized-transferred T-lymphocytes seemed to be the induction of cytotoxic macrophages in the (naive) recipient mice, as the peritoneal macrophages collected from the recipient mice 7 days after i.p. injection of a mixture of sensitized T-cells and tumor cells were cytotoxic. Purified peritoneal T-lymphocytes collected from these recipient mice were able to induce macrophage cytotoxicity in vitro but expressed no cytotoxic T-cell activity. In conclusion, our results show that in the tumor system used, tumor neutralization after transfer of sensitized lymphocytes is not dependent on the presence of cytotoxic T-lymphocytes. Lymphocytes with the strongest potency to render macrophages cytotoxic (in vitro and in vivo) also induce the best tumor neutralization in vivo, suggesting an important role for host macrophages as antitumor effector cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.