scholarly journals Direct CD4 Help Provision following Interaction of Memory CD4 and CD8 T Cells with Distinct Antigen-Presenting Dendritic Cells

2010 ◽  
Vol 185 (2) ◽  
pp. 1028-1036 ◽  
Author(s):  
Marie-Ghislaine de Goër de Herve ◽  
Bamory Dembele ◽  
Mélissa Vallée ◽  
Florence Herr ◽  
Anne Cariou ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cd4 Help ◽  
Antigen Presenting

scholarly journals 714 Selective expansion of antigen-specific CD8 T cells with engineered antigen presenting exosome

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A743-A743
Author(s):  
Tomoyoshi Yamano ◽  
Xiabing Lyu ◽  
Rikinari Hanayama
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Costimulatory Molecule ◽  
Animal Experiments ◽  
Surface Proteins ◽  
Hek293 Cells ◽  
Target Cells ◽  
Single Chain ◽  
Antigen Presenting

BackgroundExosomes are vesicular granules of about 100 nm and are secreted by many types of cells. Exosomes contain various proteins, lipids, and RNAs that are transported to target cells which induce functional and physiological changes. Exosomes are promising nano-vesicles for clinical application, owing to their high biocompatibility, low immunogenicity, and high drug delivery efficacy. Recent studies have demonstrated that exosomes from tumor cells or antigen presenting cells (APCs) regulate immune responses. Tumor derived exosomes express PD-L1 on their surface and suppress tumor immunity systemically. On the other hand, mature dendritic cells derived exosomes exert immune activation, and tumor immunotherapy using DCs exosome has been developed. However, few studies have been found to exert a significant effect on cancer treatment, may be because of low expression of costimulatory molecules and lack of cytokines on DCs derived exosomes.MethodsIt has been demonstrated that GFP can be conveyed into exosomes by conjugating GFP with tetraspanins, exosome-specific surface proteins. First, we generated a tetraspanin fusion protein with a single-chain MHCI trimer (scMHCI). IL-2 is inserted on the second extracellular loop of CD81, allowing robust and functional expression of IL-2 on the exosome. We collected exosomes from HEK293 cells culture, which stably express scMHCI-CD81-IL2 and CD80-MFGE8, and used as Antigen-presenting exosome(AP-Exo).ResultsAP-Exo expresses high expression of MHCI-peptide complex, costimulatory molecule, and cytokine, activating cognate CD8 T cells as dendritic cells do. AP-Exo selectively delivered co-stimulation and IL-2 to antigen-specific CD8 T cells, resulting in a massive expansion of antigen-specific CD8 T cells without severe adverse effects in mice. AP-Exo can expand endogenous tumor-specific CD8 T cells and induce the potent anti-tumor effect.ConclusionsOur strategy for building engineered exosomes that work like APCs might develop novel methods for cancer immunotherapy.Ethics ApprovalAll mice were housed in a specific pathogen-free facility, and all animal experiments were performed according to a protocol approved by Kanazawa University, Kanazawa, Japan.

scholarly journals Fcγ Receptor Type I (CD64)-Mediated Impairment of the Capacity of Dendritic Cells to Activate Specific CD8 T Cells by IgG-opsonized Friend Virus

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 145 ◽  
Author(s):  
Zoltán Bánki ◽  
Roland Werner ◽  
Lydia Riepler ◽  
Annika Rössler ◽  
Brigitte Müllauer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Friend Virus ◽  
Fcγ Receptor ◽  
Fcγ Receptors ◽  
Viral Antigens ◽  
Antigen Presenting

Dendritic cells (DCs) express Fcγ receptors (FcγRs) for the binding immune complexes (ICs) consisting of IgG and antigens (Ags). IC–FcγR interactions have been demonstrated to enhance activation and antigen-presenting functions of DCs. Utilizing Friend virus (FV), an oncogenic mouse retrovirus, we investigated the effect of IgG-opsonization of retroviral particles on the infection of DCs and the subsequent presentation of viral antigens by DCs to virus-specific CD8 T cells. We found that opsonization by virus-specific non-neutralizing IgG abrogated DC infection and as a consequence significantly reduced the capacity of DCs to activate virus-specific CD8 T cells. Effects of IgG-opsonization were mediated by the high-affinity FcγR type I, CD64, expressed on DCs. Our results suggest that different opsonization patterns on the retroviral surface modulate infection and antigen-presenting functions of DCs, whereby, in contrast to complement, IgG reduces the capacity of DCs to activate cytotoxic T cell (CTL) responses.

Secretion of bioactive interleukin-1β by dendritic cells is modulated by interaction with antigen specific T cells

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3809-3815 ◽  
Author(s):  
Stefania Gardella ◽  
Cristina Andrei ◽  
Sara Costigliolo ◽  
Lucia Olcese ◽  
M. Raffaella Zocchi ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 1Β ◽  
T Lymphocyte Subsets ◽  
Cd8 T Lymphocyte ◽  
Human Dendritic Cells ◽  
Antigen Presenting

The role of interleukin-1β (IL-1β) as a regulator of the immune response, although extensively investigated, is still debated. We then studied the expression of IL-1β by human dendritic cells (DCs), the professional antigen presenting cells, and its modulation during immune reactions in vitro. Our results show that, on maturation or tetanus toxoid presentation to specific CD4+ CD40L+T lymphocytes, DCs begin to accumulate IL-1β precursor (pro–IL-1β) but do not secrete bioactive IL-1β. In contrast, interaction with alloreactive T cells results in both stimulation of pro–IL-1β synthesis and secretion of processed isoforms of the cytokine, that display biologic activity. Both CD4+ and CD8+ subsets of allospecific T lymphocytes are required: CD4+ T cells drive the synthesis of pro–IL-1β through CD40 engagement but have no effects on pro–IL-1β processing; CD8+ T cells, unable to induce synthesis of pro–IL-1β per se, are responsible for the generation of mature IL-1β by pro–IL-1β–producing DCs. Interleukin-1β–converting enzyme (ICE) inhibitors do not prevent the recovery of IL-1β bioactivity after allorecognition, indicating that allospecific CD8+ T cells may induce the release of bioactive IL-1β via mechanism(s) other than ICE activation. Altogether, these findings suggest that CD4+ and CD8+ T-lymphocyte subsets have distinct roles in the induction of IL-1β secretion by DCs and support the hypothesis that IL-1β plays a role in cell-mediated immune responses.

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses

Blood ◽  
2013 ◽  
Vol 122 (6) ◽  
pp. 932-942 ◽  
Author(s):  
Giulia Nizzoli ◽  
Jana Krietsch ◽  
Anja Weick ◽  
Svenja Steinfelder ◽  
Federica Facciotti ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Key Points ◽  
Cytotoxic Molecules ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting

Key Points CD1c+ DC but not BDCA-3+ DC or other antigen-presenting cells secrete high amounts of bioactive IL-12. CD1c+ DC efficiently cross-present antigens, prime CD8+ T cells, and induce the highest levels of cytotoxic molecules.

Secretion of bioactive interleukin-1β by dendritic cells is modulated by interaction with antigen specific T cells

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3809-3815 ◽  
Author(s):  
Stefania Gardella ◽  
Cristina Andrei ◽  
Sara Costigliolo ◽  
Lucia Olcese ◽  
M. Raffaella Zocchi ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 1Β ◽  
T Lymphocyte Subsets ◽  
Cd8 T Lymphocyte ◽  
Human Dendritic Cells ◽  
Antigen Presenting

Abstract The role of interleukin-1β (IL-1β) as a regulator of the immune response, although extensively investigated, is still debated. We then studied the expression of IL-1β by human dendritic cells (DCs), the professional antigen presenting cells, and its modulation during immune reactions in vitro. Our results show that, on maturation or tetanus toxoid presentation to specific CD4+ CD40L+T lymphocytes, DCs begin to accumulate IL-1β precursor (pro–IL-1β) but do not secrete bioactive IL-1β. In contrast, interaction with alloreactive T cells results in both stimulation of pro–IL-1β synthesis and secretion of processed isoforms of the cytokine, that display biologic activity. Both CD4+ and CD8+ subsets of allospecific T lymphocytes are required: CD4+ T cells drive the synthesis of pro–IL-1β through CD40 engagement but have no effects on pro–IL-1β processing; CD8+ T cells, unable to induce synthesis of pro–IL-1β per se, are responsible for the generation of mature IL-1β by pro–IL-1β–producing DCs. Interleukin-1β–converting enzyme (ICE) inhibitors do not prevent the recovery of IL-1β bioactivity after allorecognition, indicating that allospecific CD8+ T cells may induce the release of bioactive IL-1β via mechanism(s) other than ICE activation. Altogether, these findings suggest that CD4+ and CD8+ T-lymphocyte subsets have distinct roles in the induction of IL-1β secretion by DCs and support the hypothesis that IL-1β plays a role in cell-mediated immune responses.

scholarly journals Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8+ T cells and dendritic cells

Blood ◽  
2013 ◽  
Vol 121 (26) ◽  
pp. 5184-5191 ◽  
Author(s):  
Catherine E. Terrell ◽  
Michael B. Jordan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Physiological Mechanism ◽  
Cd8 T Cell ◽  
Key Points ◽  
Antigen Presenting

Key PointsDefects in perforin and related genes lead to abnormal T-cell activation and are associated with HLH. The physiological mechanism by which perforin protects from HLH involves CD8+ T-cell elimination of rare antigen-presenting dendritic cells.

scholarly journals Cutting Edge: Cognate CD4 Help Promotes Recruitment of Antigen-Specific CD8 T Cells around Dendritic Cells

2006 ◽  
Vol 177 (3) ◽  
pp. 1406-1410 ◽  
Author(s):  
Hélène Beuneu ◽  
Zacarias Garcia ◽  
Philippe Bousso
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cutting Edge ◽  
Cd4 Help

scholarly journals Uncoupling of Proliferative Potential and Gain of Effector Function by CD8+ T Cells Responding to Self-Antigens

2002 ◽  
Vol 196 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Javier Hernández ◽  
Sandra Aung ◽  
Kristi Marquardt ◽  
Linda A. Sherman
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Effector Function ◽  
Proliferative Potential ◽  
Peripheral Tissues ◽  
Cd8 Cells ◽  
Cd4 Help ◽  
Antigen Presenting ◽  
Secondary Lymphoid Organs ◽  
Self Antigens

Professional antigen-presenting cells (APCs) are capable of transporting self-antigens from peripheral tissues to secondary lymphoid organs where they are presented to potentially autoreactive CD8+ T cells. In the absence of an inflammatory response, this results in immune tolerance. The presence of activated, antigen-specific CD4+ T cells converts this tolerogenic encounter into an immunogenic one by promoting extensive proliferation of CD8+ T cells and their development into effectors. Surprisingly, activation of APCs with an agonistic antibody specific for CD40 could not substitute for CD4+ help in this task. Anti-CD40 induced recruitment of dendritic cells expressing high levels of B7 costimulatory molecules into the lymph nodes, which in turn, greatly enhanced activation and expansion of CD8+ T cells. However, these activated CD8+ cells did not demonstrate effector function. We conclude that proliferative potential and gain of effector function are separable events in the differentiation program of CD8+ T cells.

scholarly journals Cognate CD4+ Help Elicited by Resting Dendritic Cells Does Not Impair the Induction of Peripheral Tolerance in CD8+ T Cells

2007 ◽  
Vol 178 (4) ◽  
pp. 2094-2103 ◽  
Author(s):  
Raymond J. Steptoe ◽  
Janine M. Ritchie ◽  
Nicholas S. Wilson ◽  
Jose A. Villadangos ◽  
Andrew M. Lew ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Peripheral Tolerance ◽  
Cd4 Help
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