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 Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

1998 ◽  
Vol 187 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Sarah E. Townsend ◽  
Christopher C. Goodnow
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cell Fate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

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.

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1727-1734 ◽  
Author(s):  
Éric Aubin ◽  
Réal Lemieux ◽  
Renée Bazin
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
In Vivo Model ◽  
Cell Responses ◽  
Antigen Presenting

Abstract Several clinical studies done with intravenous immunoglobulin (IVIg)–treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcγRIIb-independent, suggesting that IVIg must interfere with activating FcγRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.

scholarly journals Bone Marrow–Derived Antigen-Presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (Tap)-Dependent and -Independent Pathways of Antigen Presentation

2000 ◽  
Vol 192 (8) ◽  
pp. 1143-1150 ◽  
Author(s):  
Luis J. Sigal ◽  
Kenneth L. Rock
Keyword(s):  
Bone Marrow ◽  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Lymphocytic Choriomeningitis ◽  
Ctl Response ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Ctl Responses

Bone marrow (BM)-derived professional antigen-presenting cells (pAPCs) are required for the generation of cytotoxic T lymphocyte (CTL) responses to vaccinia virus and poliovirus. Furthermore, these BM-derived pAPCs require a functional transporter associated with antigen presentation (TAP). In this report we analyze the requirements for BM-derived pAPCs and TAP in the initiation of CTL responses to lymphocytic choriomeningitis virus (LCMV) and influenza virus (Flu). Our results indicate a requirement for BM-derived pAPCs for the CTL responses to these viruses. However, we found that the generation of CTLs to one LCMV epitope (LCMV nucleoprotein 396–404) was dependent on BM-derived pAPCs but, surprisingly, TAP independent. The study of the CTL response to Flu confirmed the existence of this BM-derived pAPC-dependent/TAP-independent CTL response and indicated that the TAP-independent pathway is ∼10–300-fold less efficient than the TAP-dependent pathway.

scholarly journals Delivery of Multiple Epitopes by Recombinant Detoxified Adenylate Cyclase of Bordetella pertussisInduces Protective Antiviral Immunity

2001 ◽  
Vol 75 (16) ◽  
pp. 7330-7338 ◽  
Author(s):  
Catherine Fayolle ◽  
Adriana Osickova ◽  
Radim Osicka ◽  
Thomas Henry ◽  
Marie-Jésus Rojas ◽  
...  
Keyword(s):  
T Cell ◽  
Adenylate Cyclase ◽  
Catalytic Domain ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
T Cell Epitopes ◽  
Antigen Presenting ◽  
Ctl Responses

ABSTRACT CyaA, the adenylate cyclase toxin from Bordetella pertussis, can deliver its N-terminal catalytic domain into the cytosol of a large number of eukaryotic cells and particularly into professional antigen-presenting cells. We have previously identified within the primary structure of CyaA several permissive sites at which insertion of peptides does not alter the ability of the toxin to enter cells. This property has been exploited to design recombinant CyaA toxoids capable of delivering major histocompatibility complex (MHC) class I-restricted CD8+ T-cell epitopes into antigen-presenting cells and to induce specific CD8+cytotoxic T-lymphocyte (CTL) responses in vivo. Here we have explored the capacity of the CyaA vector carrying several different CD8+ T-cell epitopes to prime multiple CTL responses. The model vaccine consisted of a polyepitope made of three CTL epitopes from lymphocytic choriomeningitis virus (LCMV), the V3 region of human immunodeficiency virus gp120, and chicken ovalbumin, inserted at three different sites of the catalytic domain of genetically detoxified CyaA. Each of these epitopes was processed on delivery by CyaA and presented in vitro to specific T-cell hybridomas. Immunization of mice by CyaA toxoids carrying the polyepitope lead to the induction of specific CTL responses for each of the three epitopes, as well as to protection against a lethal viral challenge. Moreover, mice primed against the vector by mock CyaA or a recombinant toxoid were still able to develop strong CTL responses after subsequent immunization with a recombinant CyaA carrying a foreign CD8+ CTL epitope. These results highlight the potency of the adenylate cyclase vector for induction of protective CTL responses with multiple specificity and/or broad MHC restriction.

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
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