25 research outputs found
T cell vaccination induces the elimination of EAE effector T cells: Analysis using GFP-transduced, encephalitogenic T cells
No full textT cell vaccination (TCV) with irradiated encephalitogenic T cells induces resistance to EAE. However, the fate of the encephalitogenic T cells in vivo following TCV has yet to be studied. Here we used anti-MBP encephalitogenic T cells that were transduced to express GFP to study the effects of TCV on these cells. In naive rats or in control-vaccinated (Ova-GFP) rats injected i.v. with GFP-labeled effector cells, high numbers of effector T cells were found along with macrophages, CD8 T cells and Non-GFP CD4 cells in the spleens, parathymic lymph nodes (PTLN) and spinal cords. In contrast, the recipients that had been treated with TCV (anti-MBP T-cell lines) showed few if any GFP-labeled effector T cells throughout the disease (day 1-8) and their spinal cords were almost clear of macrophages, CD4 and CD8 cells. Splenocytes in the control groups secreted IFN gamma in response to MBP and showed high numbers of IFN gamma secreting CD4 and CD8 cells in their spinal cords at the disease peak. In the TCV-protected groups, splenocytes showed no reactivity to MBP but secreted IFN gamma in response to irradiated encephalitogenic T cells - an anti-idiotypic response. Thus. TCV leads to a marked decrease in the numbers of effector T cells in the CNS and lymphoid organs, to a marked reduction in the Th1 cytokine producing cells in the CNS, and to the appearance of T cells responsive to the anti-MBP effector T cells. (C) 2010 Elsevier Ltd. All rights reserved
Abstract 617: Evaluating the in-vitro effects of tumor treating fields on T cell responses
No full textAbstract
BACKGROUND: Tumor Treating Fields (TTFields) are low-intensity electrical fields that target proliferating cells by hindering formation of mitotic spindle and translocation of charged organelles. TTFields have been recently approved for the treatment of both recurrent and newly diagnosed Glioblastoma (GBM). Immunotherapeutic approaches for treatment of GBM are considered promising, and multiple strategies are currently being evaluated in basic research and clinical trials. Combining TTFields and immune-based therapies is a rational approach as they possess markedly different mechanisms of action (MOA). Conversely, TTFields may potentially abrogate various cellular functions required for effective T cell responses. We performed an in-vitro evaluation on the effect of TTFields on select human T cell functions that are pivotal for an effective anti-tumoral response. The study objective was to evaluate the potential compatibility between immune-based therapies and TTFields. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors. Cells were cultured under normal versus TTFields conditions using the inovitro TTFields system, either with or without Phytohemaglutenin (PHA - a super antigen). Cellular responses were monitored using an 8-color flow cytometry panel that concurrently evaluated proliferation (CFSE dilution), cytokine secretion (IFNγ), cytotoxic degranulation (CD107a surface presentation), and T cell activation/ exhaustion (PD1 expression). The effect on T cell viability was assessed in a separate assay, by comparing the live-to-dead ratio of cells cultured in normal versus TTFields settings.
RESULTS: TTFields did not alter the functionality of non-activated T cells. Viable PHA-activated T cells cultured under TTFields exhibited no change in PD1 up-regulation, IFNγ secretion and CD107a surface-expression. The T cells exhibited reduced proliferation, which is in line with the known MOA of TTFields. As the presence of polyfunctional T cells is associated with effective anti-tumoral responses, a single-cell level polyfunctionality analysis of activated T cells was performed. The analysis demonstrated that under TTFields conditions non proliferating cells retained all other combinations of immune functions. TTFields were found to have a minor effect on the viability of un-activated T cells. In activated cells, there was a moderate effect on cells that did not attempt to proliferate, but TTFields substantially reduced the viability rate of cells that had proliferated. These findings were true for both helper and cytotoxic T cells.
CONCLUSIONS: Pivotal T-cell response parameters, but not proliferation, were found to be unhindered by TTFields. Our current data suggests that the integration of TTFields with various immunotherapeutic approaches may be a rational strategy to explore for the treatment of brain tumors.
Citation Format: Gil Diamant, Ilan Volovitz, Zvi Ram. Evaluating the in-vitro effects of tumor treating fields on T cell responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 617. doi:10.1158/1538-7445.AM2017-617</jats:p
Abstract B117: Evaluating the in vitro effects of tumor-treating fields on T-cell responses
No full textImmune Responses to SARS-CoV2 Mirror Societal Responses to COVID-19: Identifying Factors Underlying a Successful Viral Response
No full textThe adaptive immune system was sculpted to protect individuals, societies, and species since its inception, developing effective strategies to cope with emerging pathogens. Here, we show that similar successful or failed dynamics govern personal and societal responses to a pathogen as SARS-CoV2. Understanding the self-similarity between the health-protective measures taken to protect the individual or the society, help identify critical factors underlying the effectiveness of societal response to a pathogenic challenge. These include (1) the quick employment of adaptive-like, pathogen-specific strategies to cope with the threat including the development of “memory-like responses”; (2) enabling productive coaction and interaction within the society by employing effective decision-making processes; and (3) the quick inhibition of positive feedback loops generated by hazardous or false information. Learning from adaptive anti-pathogen immune responses, policymakers and scientists could reduce the direct damages associated with COVID-19 and avert an avoidable “social cytokine storm” with its ensuing socioeconomic damage
Abstract A021: Vaccination with autologous, nonattenuated, live glioblastoma cells induces potent peripheral and intratumoral anti-tumoral responses: A first-in-human study
No full textThe mechanisms controlling NK cell autoreactivity in TAP2-deficient patients
No full textThe killing of natural killer (NK) cells is regulated by activating and inhibitory NK receptors that recognize mainly class I major histocompatibility complex (MHC) proteins. In transporter associated with antigen processing (TAP2)–deficient patients, killing of autologous cells by NK cells is therefore expected. However, none of the TAP2-deficient patients studied so far have suffered from immediate NK-mediated autoimmune manifestations. We have previously demonstrated the existence of a novel class I MHC–independent inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) interactions. Here, we identified 3 new siblings suffering from TAP2 deficiency. NK cells derived from these patients express unusually high levels of the various killer cell inhibitory receptors (KIRs) and the CEACAM1 protein. Importantly, the patients' NK cells use the CEACAM1 protein to inhibit the killing of tumor and autologous cells. Finally, we show that the function of the main NK lysis receptor, NKp46, is impaired in these patients. These results indicate that NK cells in TAP2-deficient patients have developed unique mechanisms to reduce NK killing activity and to compensate for the lack of class I MHC–mediated inhibition. These mechanisms prevent the attack of self-cells by the autologous NK cells and explain why TAP2-deficient patients do not suffer from autoimmune manifestations in early stages of life. <br/
