scholarly journals S100A4 exerts robust mucosal adjuvant activity for co-administered antigens in mice

2022 ◽  
Author(s):  
Arka Sen Chaudhuri ◽  
Yu-Wen Yeh ◽  
Jia-Bin Sun ◽  
Olifan Zewdie ◽  
Tao Jin ◽  
...  
Keyword(s):  
Germinal Center ◽  
Calcium Binding ◽  
Cytotoxic T Cell ◽  
Adjuvant Activity ◽  
Mucosal Adjuvant ◽  
Wide Range ◽  
Center Activity ◽  
Mucosal Vaccines ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting

The lack of clinically applicable mucosal adjuvants is a major hurdle in designing effective mucosal vaccines. We hereby report that the calcium-binding protein S100A4, which regulates a wide range of biological functions, is a potent mucosal adjuvant in mice for co-administered antigens, including the SARS-CoV-2 spike protein, with comparable or even superior efficacy as cholera toxin but without causing any adverse reactions. Intranasal immunization with recombinant S100A4 elicited antigen-specific antibody and pulmonary cytotoxic T cell responses, and these responses were remarkably sustained for longer than six months. As a self-protein, S100A4 did not stimulate antibody responses against itself, a quality desired of adjuvants. S100A4 prolonged nasal residence of intranasally delivered antigens and promoted migration of antigen-presenting cells. S100A4-pulsed dendritic cells potently activated cognate T cells. Furthermore, S100A4 induced strong germinal center responses revealed by both microscopy and mass spectrometry, a novel technique for measuring germinal center activity. In conclusion, S100A4 may be a promising adjuvant in formulating mucosal vaccines, including vaccines against pathogens that infect via the respiratory tract, such as SARS-CoV-2.

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.

scholarly journals Requirements for Bone Marrow–Derived Antigen-Presenting Cells in Priming Cytotoxic T Cell Responses to Intracellular Pathogens

2000 ◽  
Vol 192 (8) ◽  
pp. 1135-1142 ◽  
Author(s):  
Laurel L. Lenz ◽  
Eric A. Butz ◽  
Michael J. Bevan
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Antigen Presentation ◽  
Antigen Presenting Cells ◽  
Cytotoxic T Cell ◽  
Chimeric Mice ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting ◽  
Ctl Responses

Bone marrow (BM)-derived antigen-presenting cells (APCs) are potent stimulators of T cell immune responses. We investigated the requirements for antigen presentation by these cells in priming cytotoxic T lymphocyte (CTL) responses to intracellular bacterial and viral pathogens. [Parent→F1] radiation BM chimeras were constructed using C57BL/6 donors and (C57BL/6 × BALB/c)F1 recipients. Infection of chimeric mice with either Listeria monocytogenes or vaccinia virus expressing the nucleoprotein (NP) antigen from lymphocytic choriomeningitis virus (LCMV) primed H2-Db–restricted, but not H2-Kd–restricted CTL responses, demonstrating the requirement for BM-derived APCs for successful priming of CTL responses to these pathogens. Surprisingly, this did not hold true for chimeric mice infected with LCMV itself. LCMV-infected animals developed strong CTL responses specific for both H2-Db– and H2-Ld–restricted NP epitopes. These findings indicate that in vivo priming of CTL responses to LCMV is remarkably insensitive to deficiencies in antigen presentation by professional BM-derived APCs.

scholarly journals Artificial human antigen-presenting cells are superior to dendritic cells at inducing cytotoxic T-cell responses

Immunology ◽  
2017 ◽  
Vol 152 (3) ◽  
pp. 462-471 ◽  
Author(s):  
Hua Li ◽  
Shengwen Shao ◽  
Jianshu Cai ◽  
Danielle Burner ◽  
Lingeng Lu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses ◽  
Antigen Presenting

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.

scholarly journals Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked

2005 ◽  
Vol 86 (2) ◽  
pp. 323-331 ◽  
Author(s):  
Peter Vanlandschoot ◽  
Freya Van Houtte ◽  
Peter Ulrichts ◽  
Jan Tavernier ◽  
Geert Leroux-Roels
Keyword(s):  
Hepatitis B ◽  
Vaccine Development ◽  
Careful Examination ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
B Virus ◽  
Natural Hosts ◽  
Cytotoxic T Cell Responses ◽  
Underlying Mechanisms ◽  
Antigen Presenting

The nucleocapsid of hepatitis B virus (HBV) allows insertions of heterologous peptides and even complete proteins. Because of its outstanding capacity to induce B-cell, T-helper and cytotoxic T-cell responses, this structure is considered to be an important instrument for future vaccine development. Most of the evidence for the unique immunogenic qualities of nucleocapsids has been generated in mice, which are not natural hosts of HBV. Moreover, most nucleocapsid preparations used in these studies were produced in a recombinant manner in Escherichia coli. Such preparations have been shown to contain lipopolysaccharide (LPS). Not unexpectedly, it is shown here that contaminating LPS, rather than the nucleocapsid structure itself, is responsible for the activation of human antigen-presenting cells. Careful examination of the literature dealing with the immunogenicity of HBV nucleocapsids suggests that the possible presence of LPS has been largely ignored or underestimated in several studies. This raises doubts on some of the underlying mechanisms that have been proposed to explain the unique immunogenicity of the HBV nucleocapsid.

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