scholarly journals Heat Shock Treatment of Tumor Lysate-Pulsed Dendritic Cells Enhances Their Capacity to Elicit Antitumor T Cell Responses against Medullary Thyroid Carcinoma

2006 ◽  
Vol 91 (11) ◽  
pp. 4571-4577 ◽  
Author(s):  
Thomas Bachleitner-Hofmann ◽  
Michaela Strohschneider ◽  
Peter Krieger ◽  
Monika Sachet ◽  
Peter Dubsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Tumor Cells ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Tumor Lysate ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

Abstract Background: In vitro and in vivo studies have shown that dendritic cells (DCs) can stimulate antitumor T cell responses against medullary thyroid carcinoma (MTC). However, despite promising results in selected cases, the clinical efficacy of DC immunotherapy in patients with MTC has been limited. Recently, it has been demonstrated in mice that heat shock enhances the capacity of bone-marrow-derived DCs to stimulate antigen-specific T cells. The aim of our investigations was to evaluate whether heat shock also increases the capacity of human monocyte-derived DCs to stimulate antitumor T cell responses against MTC tumor cells. Methods: DCs from six patients with metastatic MTC were pulsed with tumor lysate derived from allogeneic MTC tumor cells and were heat shocked for 12 h at 40 C or kept at 37 C. Thereafter, the DCs were matured and cocultured with T cells. Finally, the cytotoxic activity of T cells against MTC tumor cells was measured in vitro. Results: In all patient samples, cytotoxic T cell responses against MTC tumor cells could be induced. Notably, heat-shocked DCs were more potent stimulators of cytotoxic T cell responses than control DCs, with T cells stimulated with heat-shocked DCs displaying a significantly increased cytotoxic activity against MTC tumor cells as compared with T cells stimulated with control DCs. In none of the experiments was a cytotoxic T cell response against unrelated pancreatic tumor cells (PANC-1) observed, using both control and heat-shocked DCs. Conclusions: Our study shows that heat-shocking DCs may be a valuable strategy to increase the immunostimulatory capacity of DCs used for immunotherapy of MTC.

Dendritic Cells Reconstituted with a Human Heparanase Gene Induce Potent Cytotoxic T-Cell Responses against Gastric Tumor Cells in vitro

Tumor Biology ◽  
2007 ◽  
Vol 28 (4) ◽  
pp. 238-246 ◽  
Author(s):  
Yong-Guo Cai ◽  
Dian-Chun Fang ◽  
Ling Chen ◽  
Xu-Dong Tang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Tumor Cells ◽  
T Cell Responses ◽  
Gastric Tumor ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

scholarly journals Virus-Specific CD4+ and CD8+ Cytotoxic T-Cell Responses and Long-Term T-Cell Memory in Individuals Vaccinated against Polio

2005 ◽  
Vol 79 (10) ◽  
pp. 5988-5995 ◽  
Author(s):  
Rahnuma Wahid ◽  
Martin J. Cannon ◽  
Marie Chow
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

ABSTRACT The presence of poliovirus (PV)-specific CD4+ T cells in individuals vaccinated against polio has been shown, but CD8+ T-cell responses have not been described. Here, we functionally characterize the CD4+ T-cell response and show for the first time that dendritic cells and macrophages can stimulate PV-specific CD8+ T-cell responses in vitro from vaccinees. Both CD4+ T and CD8+ T cells secrete gamma interferon in response to PV antigens and are cytotoxic via the perforin/granzyme B-mediated pathway. Furthermore, the T cells also recognize and kill Sabin 1 vaccine-infected targets. The macrophage-stimulated CD4+ T and CD8+ T cells most likely represent memory T cells that persist for long periods in vaccinated individuals. Thus, immunity to PV vaccination involves not only an effective neutralizing antibody titer but also long-term CD4+ and CD8+ cytotoxic T-cell responses.

scholarly journals Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex.

1979 ◽  
Vol 149 (1) ◽  
pp. 150-157 ◽  
Author(s):  
P C Doherty ◽  
J C Bennink
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Antigen Complex ◽  
Infected Cells ◽  
Cytotoxic T Cell Responses

BALB/c (H-2Kd-Dd) spleen and lymph node populations were specifically depleted of alloreactive potential by filtration through H-2 different, irradiated recipients. These negatively selected T cells were then stimulated with vaccinia virus in mice expressing the foreign H-2 determinants encountered previously in the filter environment. Strong virus-immune cytotoxic T-cell responses were seen in the context of H-2Kk and H-2Ks, but not 2H-2Kb. The T cells generated were not cross-reactive for the H-2Kk and H-2Kd alleles, and responsiveness was independent of concurrent presence of effector populations operating at H-2D. These findings are consisent with the idea that recognition is mediated via a complex receptor, part of which is specific for virus and part for self H-2. The capacity to interact with allogeneic, virus-infected cells may then reflect aberrant recognition of a virus-H-2-antigen complex by this single, large binding site. For instance, the T cell which would normally recognize H-2Kd-virus x, or H-2Dd-minor histocompatibility antigen Z, may now show specificity for H-2Kk-vaccinia virus. Implications for both the selective role of the thymus and for mechanisms of tolerance are discussed.

scholarly journals Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3546-3552 ◽  
Author(s):  
Christian Schütz ◽  
Martin Fleck ◽  
Andreas Mackensen ◽  
Alessia Zoso ◽  
Dagmar Halbritter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Fas Ligand ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting

Abstract Several cell-based immunotherapy strategies have been developed to specifically modulate T cell–mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell–based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)–dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of κaAPCs and independent of activation-induced cell death (AICD). κaAPCs represent a novel technology that can control T cell–mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.

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