scholarly journals An Artificial Antigen-presenting Cell with Paracrine Delivery of IL-2 Impacts the Magnitude and Direction of the T Cell Response

2011 ◽  
Vol 286 (40) ◽  
pp. 34883-34892 ◽  
Author(s):  
Erin R. Steenblock ◽  
Tarek Fadel ◽  
Michael Labowsky ◽  
Jordan S. Pober ◽  
Tarek M. Fahmy
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
Antigen Presenting

The ability of Ia and H-2Kk-bearing membranes to replace the antigen-presenting cell in an H-2Kkallogeneic cytotoxic T cell response

1985 ◽  
Vol 15 (10) ◽  
pp. 1013-1018 ◽  
Author(s):  
Ofra Weinberger ◽  
Steven H. Herrmann ◽  
Julia L. Greenstein ◽  
Matthew F. Mescher ◽  
Steven J. Burakoff
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Antigen Presenting Cell ◽  
Antigen Presenting

scholarly journals Neutrophils acquire antigen-presenting cell features after phagocytosis of IgG-opsonized erythrocytes

2019 ◽  
Vol 3 (11) ◽  
pp. 1761-1773 ◽  
Author(s):  
Sanne M. Meinderts ◽  
Gabriella Baker ◽  
Stan van Wijk ◽  
Boukje M. Beuger ◽  
Judy Geissler ◽  
...  
Keyword(s):  
T Cell ◽  
Respiratory Burst ◽  
Cell Response ◽  
T Cell Response ◽  
Human Neutrophils ◽  
Antigen Presenting Cell ◽  
Mhc Ii ◽  
Class Ii Mhc ◽  
Antimicrobial Function ◽  
Antigen Presenting

Abstract Neutrophils are particularly well known for their antimicrobial function. Although historically they are regarded as strictly a phagocyte of the innate immune system, over time it has become clear that neutrophils are versatile cells with numerous functions including innate and adaptive immune regulation. We have previously described a role for human neutrophils in antibody-mediated red blood cell (RBC) clearance. Under homeostatic conditions, neutrophils do not take up RBCs. Yet, when RBCs are immunoglobulin G (IgG) opsonized, which can occur in alloimmunization or autoimmunization reactions, neutrophils can effectively phagocytose RBCs. In the present study, we show that human neutrophils acquire an antigen-presenting cell (APC) phenotype following RBC phagocytosis. Subsequent to RBC phagocytosis, neutrophils expressed major histocompatibility complex class II (MHC-II) and costimulatory molecules such as CD40 and CD80. Moreover, in classical APCs, the respiratory burst is known to regulate antigen presentation. We found that the respiratory burst in neutrophils is reduced after IgG-mediated RBC phagocytosis. Additionally, following RBC phagocytosis, neutrophils were demonstrated to elicit an antigen-specific T-cell response, using tetanus toxoid (TT) as an antigen to elicit an autologous TT-specific CD4+ T-cell response. Lastly, although the “don’t eat me” signal CD47 is known to have a powerful restrictive role in the activation of immunity against RBCs in dendritic cells, CD47 does not seem to have a significant effect on the antigen-presenting function of neutrophils in this context. Overall, these findings reveal that besides their classical antimicrobial role, neutrophils show plasticity in their phenotype.

scholarly journals Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+ T Cells to the Brain during Theiler's Virus Infection

2005 ◽  
Vol 79 (5) ◽  
pp. 3063-3070 ◽  
Author(s):  
Yanice V. Mendez-Fernandez ◽  
Michael J. Hansen ◽  
Moses Rodriguez ◽  
Larry R. Pease
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Lymphoid Organs ◽  
Antigen Presenting Cell ◽  
Antigen Presenting ◽  
The Brain

ABSTRACT Theiler's murine encephalomyelitis virus (TMEV) infection of the brain induces a virus-specific CD8+ T-cell response in genetically resistant mice. The peak of the immune response to the virus occurs 7 days after infection, with an immunodominant CD8+ T-cell response against a VP2-derived capsid peptide in the context of the Db molecule. The process of activation of antigen-specific T cells that migrate to the brain in the TMEV model has not been defined. The site of antigenic challenge in the TMEV model is directly into the brain parenchyma, a site that is considered immune privileged. We investigated the hypothesis that antiviral CD8+ T-cell responses are initiated in situ upon intracranial inoculation with TMEV. To determine whether a brain parenchymal antigen-presenting cell is responsible for the activation of virus-specific CD8+ T cells, we evaluated the CD8+ T-cell response to the VP2 peptide in bone marrow chimeras and mutant mice lacking peripheral lymphoid organs. The generation of the anti-TMEV CD8+ T-cell response in the brain requires priming by a bone marrow-derived antigen-presenting cell and the presence of peripheral lymphoid organs. Although our results show that activation of TMEV-specific CD8+ T cells occurs in the peripheral lymphoid compartment, they do not exclude the possibility that the immune response to TMEV is initiated by a brain-resident, bone marrow-derived, antigen-presenting cell.

scholarly journals H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

1982 ◽  
Vol 156 (3) ◽  
pp. 822-833 ◽  
Author(s):  
C N Baxevanis ◽  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
Lactate Dehydrogenase ◽  
T Cell ◽  
Cell Response ◽  
Cell Types ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Th Cell ◽  
Antigen Presenting

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

scholarly journals Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Pisapia ◽  
Stefania Picascia ◽  
Federica Farina ◽  
Pasquale Barba ◽  
Carmen Gianfrani ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Differential Expression ◽  
T Cell Activation ◽  
Cell Response ◽  
Cell Activation ◽  
T Cell Response ◽  
Risk Alleles ◽  
Personalized Diagnosis ◽  
Antigen Presenting

Abstract The DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05 and HLA-DQB1*02 predisposing alleles, in trans configuration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+ T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+ T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are in cis configuration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+ T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression of DQA1*05 and DQB1*02 risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposing DQA1*05 and DQB1*02 alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+ T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.

Artificial Antigen Presenting Cell Can Be Used To Propagate Genetically Modified CD19-Specific T Cells through Chimeric Antigen Receptor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1295-1295
Author(s):  
Tontanai Numbenjapon ◽  
Lisa Marie A. Serrano ◽  
Simon Olivares ◽  
Wen-Chung Chang ◽  
Harjeet Singh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Chimeric Antigen Receptor ◽  
Cell Activation ◽  
Genetically Modified ◽  
K562 Cells ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
Antigen Presenting

Abstract The safety and feasibility of adoptive immunotherapy, using CD19-specific T cells that have been genetically modified to express a chimeric antigen receptor (CAR) and numerically expanded ex vivo, need to be addressed. Second-generation trials are being developed incorporating improvements into the design of the CAR as well as the manufacturing processes. Here we describe a platform for propagating CD19-specific T cells through an artificial antigen presenting cell (aAPC) which co-expresses CD19 and T-cell co-stimulatory molecules to provide a fully-competent T-cell activation signal leading to T-cell proliferation. K562 cells were selected as the platform for the aAPCs since (i) they have previously been used in compliance with current good manufacturing practice (cGMP), (ii) they express the desired endogenous T-cell adhesion molecules, and (iii) they fail to express classical HLA class I/II molecules and thus are not targets for a T-cell mediated allogeneic immune response. Therefore, K562 cells were genetically modified to co-express CD19 and both of the T-cell co-stimulatory molecules 4-1BBL (CD137L) and MICA. We then tested the ability of these K562 aAPCs to expand T cells expressing a new CD19-specific CAR designated CD19RCD28. This CAR utilizes a CD19-specific scFv to bind to CD19 independent of MHC and confers an activation signal to genetically modified T cells through both CD28 and CD3-ζ. The CD19RCD28+ T cells could be rapidly expanded (50-fold in 14 days) when cultured in the presence of recombinant human IL-2 and irradiated K562 aAPCs (1:50 ratio, T cell to aAPC). The use of freshly thawed aAPCs improved the practicality of using this antigen-driven expansion method in compliance with cGMP. The numerical expansion of the genetically modified T cells was associated with an increased CAR cell-surface expression, from 17 ± 11% (mean ± SD) before co-culture compared with 44 ± 8% (mean ± SD) after co-culture with the aAPCs, which is consistent with T-cell activation through the CAR. A 3H-thymidine incorporation assay was used to demonstrate that CD19 on the K562 aAPC was necessary, but not sufficient, to proliferate CD19RCD28+ T cells. Furthermore, this proliferation assay demonstrated that co-expression of both 4-1BBL (CD137L) and MICA along with CD19 resulted in the most efficient proliferation of the genetically modified T cells. The propagation of CAR+ T cells on antigen+ aAPCs may thus (i) avoid the need for allogeneic peripheral blood mononuclear feeder cells, which are expensive and time-consuming to prepare in compliance with cGMP, (ii) select in vitro for genetically modified T cells with proven CAR-dependent replicative capacity, and (iii) provide conditions for the outgrowth of subpopulations of T cells within a bulk culture that have increased transgene expression. The feasibility of this new T-cell propagation method using aAPC will be tested in the upcoming clinical trials.

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