scholarly journals Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

2016 ◽  
Vol 1 (1) ◽  
pp. aaf8759-aaf8759 ◽  
Author(s):  
Jose Marino ◽  
Mohamed H. Babiker-Mohamed ◽  
Patrick Crosby-Bertorini ◽  
Joshua T. Paster ◽  
Christian LeGuern ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Passenger Leukocytes ◽  
Alloreactive T Cell

ALLOREACTIVE T CELL RESPONSES BETWEEN HLA-IDENTICAL SIBLINGS

1985 ◽  
Vol 40 (3) ◽  
pp. 329-333 ◽  
Author(s):  
CLAUDE IRLE ◽  
PATRICK G. BEATTY ◽  
ERIC MICKELSON ◽  
E. DONNALL THOMAS ◽  
JOHN A. HANSEN
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Alloreactive T Cell

scholarly journals Alloreactive T Cell Responses and Acute Rejection of Single Class II MHC-Disparate Heart Allografts Are under Strict Regulation by CD4+CD25+ T Cells.

2005 ◽  
Vol 174 (8) ◽  
pp. 5135.2-5135 ◽  
Author(s):  
Soren Schenk ◽  
Danielle D. Kish ◽  
Chunshui He ◽  
Tarek El-Sawy ◽  
Eise Chiffoleau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Acute Rejection ◽  
T Cell Responses ◽  
Class Ii ◽  
Single Class ◽  
Cell Responses ◽  
Class Ii Mhc ◽  
Strict Regulation ◽  
Alloreactive T Cell

Spectratype Analysis of In Vitro Donor Anti-Host T Cell Repertoire Responses Predict Those of In Vivo Post-BMT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2163-2163
Author(s):  
Thea M. Friedman ◽  
Kira Goldgirsh ◽  
Jenny Zilberberg ◽  
Stephanie A. Berger ◽  
Joanne Filicko-O’Hara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Post Transplant ◽  
Cell Responses ◽  
Repertoire Analysis ◽  
Alloreactive T Cell

Abstract Immunotherapeutic strategies have gained recognition as viable alternatives to more conventional modalities for the treatment of cancer. In this regard, adoptive T cell therapy through allogeneic blood and marrow transplantation (BMT) has provided the strongest evidence that anti-tumor effects could be achieved against hematological malignancies. However, the major complications of BMT still include graft failure, opportunistic infections, disease relapse and graft-versus-host disease (GVHD). The presence of mature donor T cells in the transplant inoculum reduces the incidence of the first three complications, while unfortunately increasing the risk of GVHD, which can be directed against either HLA or minor histocompatibilty antigen (miHA) disparities. Thus, a major objective in the field has been to develop tactics that could facilitate the separation of graft-versus-tumor (GVT) effects from the deleterious effects of GVHD. One such approach would be to selectively deplete donor alloreactive T cells in the donor inoculum while allowing residual T cells to provide some protection against infection and to support a tumor-specific GVT response. For a more targeted approach, delayed donor lymphocyte infusion (DLI) of positively-selected donor GVT-reactive T cells could be used weeks to months post-transplant, if these elements were identifiable. In this regard, TCR Vβ repertoire analysis by CDR3-size spectratyping can be a powerful tool for the characterization of alloreactive T cell responses. Theoretically, molecular analysis of T cell responses in vitro, given the high sensitivity of the PCR-based spectratyping technique, should identify the most potentially critical Vβ families involved in the later development of GVHD and GVT effects in patients. To this end, we tested the hypothesis that T cell repertoire analysis of HLA-matched sibling (SIB) or matched unrelated donors (URD) from in vitro, host-stimulated, mixed lymphocyte cultures (MLC) would be predictive of the TCR-Vβ spectratype analysis of the T cell repertoire in the patient following BMT. In this study, we examined 17 patient pairs and report that for the resolvable Vβ families, we observed overall 71.2 ± 11.9% (mean ± SD.; range 40%–85%) of the in vitro anti-host T cell responses were predictive of those in the patient post-transplant. Of the 28.8% non-predictive Vβ families, 6.9 ± 6.3% (range 0%–27%) exhibited skewing in the MLC but no skewing in the patient post-transplant repertoire, 9.3 ± 6.3% (range 0%–18.8%) exhibited skewing in different peaks within the same Vβ family, and 12.5 ± 10.8% (range 0%–40%) showed skewing in the patient post-transplant and none in the MLC. Taken together, these results suggest that the in vitro MLC T cell responses show good consistency with post-transplant patient responses. Thus, in vitro spectratyping may be useful for predicting the alloreactive T cell responses involved in GVHD and could be used to guide custom-designed select Vβ family T cell-depleted transplants to improve patient outcomes. The additional advantage of this approach is that minimization of GVHD risk can be obtained without any direct knowledge of the specific miHA involved in the individual donor-patient pair.

The T-cell receptor Vβ6 gene usage in alloreactive T-cell responses

1995 ◽  
Vol 42 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Weining Hu ◽  
Cornelia M. Weyand ◽  
Jörg J. Goronzy
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Gene Usage ◽  
Alloreactive T Cell

IN VIVO-MOBILIZED KIDNEY DENDRITIC CELLS ARE FUNCTIONALLY IMMATURE, SUBVERT ALLOREACTIVE T-CELL RESPONSES, AND PROLONG ORGAN ALLOGRAFT SURVIVAL1

2004 ◽  
Vol 77 (7) ◽  
pp. 1080-1089 ◽  
Author(s):  
P. Toby H. Coates ◽  
F. Jason Duncan ◽  
Bridget L. Colvin ◽  
Zhiliang Wang ◽  
Alan F. Zahorchak ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Alloreactive T Cell

Heart Allograft Protection with Low-Dose Carbon Monoxide Inhalation: Effects on Inflammatory Mediators and Alloreactive T-cell Responses

2006 ◽  
Vol 81 (2) ◽  
pp. 220-230 ◽  
Author(s):  
Atsunori Nakao ◽  
Hideyoshi Toyokawa ◽  
Masanori Abe ◽  
Tetsuma Kiyomoto ◽  
Kiichi Nakahira ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
T Cell ◽  
Inflammatory Mediators ◽  
Low Dose ◽  
T Cell Responses ◽  
Heart Allograft ◽  
Cell Responses ◽  
Alloreactive T Cell

scholarly journals The Effects of Interferons on Allogeneic T Cell Response in GVHD: The Multifaced Biology and Epigenetic Regulations

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenchen Zhao ◽  
Yi Zhang ◽  
Hong Zheng
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Type I ◽  
Epigenetic Mechanisms ◽  
Hematopoietic Stem ◽  
Cell Responses ◽  
Alloreactive T Cells ◽  
And Function ◽  
Alloreactive T Cell

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. This beneficial effect is derived mainly from graft-versus-leukemia (GVL) effects mediated by alloreactive T cells. However, these alloreactive T cells can also induce graft-versus-host disease (GVHD), a life-threatening complication after allo-HSCT. Significant progress has been made in the dissociation of GVL effects from GVHD by modulating alloreactive T cell immunity. However, many factors may influence alloreactive T cell responses in the host undergoing allo-HSCT, including the interaction of alloreactive T cells with both donor and recipient hematopoietic cells and host non-hematopoietic tissues, cytokines, chemokines and inflammatory mediators. Interferons (IFNs), including type I IFNs and IFN-γ, primarily produced by monocytes, dendritic cells and T cells, play essential roles in regulating alloreactive T cell differentiation and function. Many studies have shown pleiotropic effects of IFNs on allogeneic T cell responses during GVH reaction. Epigenetic mechanisms, such as DNA methylation and histone modifications, are important to regulate IFNs’ production and function during GVHD. In this review, we discuss recent findings from preclinical models and clinical studies that characterize T cell responses regulated by IFNs and epigenetic mechanisms, and further discuss pharmacological approaches that modulate epigenetic effects in the setting of allo-HSCT.

scholarly journals Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses

2016 ◽  
Vol 213 (3) ◽  
pp. 415-431 ◽  
Author(s):  
Colleen M. Lau ◽  
Simone A. Nish ◽  
Nir Yogev ◽  
Ari Waisman ◽  
Steven L. Reiner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Expression Profiles ◽  
T Cell Responses ◽  
Graft Versus Host Reaction ◽  
T Cell Homeostasis ◽  
Cell Responses ◽  
Activating Mutation ◽  
A Cell ◽  
Alloreactive T Cell

A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3ITD knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3ITD/ITD mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8+ cDCs and noncanonical CD8+ cDCs were expanded and showed specific alterations in their expression profiles. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner.

Identification of Immunodominant Alloreactive T-Cell Epitopes on the Jka Red Blood Cell Protein Inducing Either Th1 or Th2 Cytokine Expression: Role of DRB1*01 Molecules in Jka Peptide Presentation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2702-2702
Author(s):  
Helene Ansart-Pirenne ◽  
Dominique Zeliszewski ◽  
Ketty Lee ◽  
Stephanie Martin-Blanc ◽  
Philippe Rouger ◽  
...  
Keyword(s):  
T Cell ◽  
Blood Cell ◽  
Red Blood Cell ◽  
T Cell Responses ◽  
Blood Group Antigen ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Peptide Presentation ◽  
Alloreactive T Cell ◽  
Th1 And Th2

Abstract Background: although antibodies implicated in red blood cell (RBC) blood group antigen alloimmunization are studied for many years, little is known about helper T cell responses that drive their production. The aim of this work was to determine T cell antigenic determinants involved in T cell responses against RBC antigens, and the subsequent patterns of stimulatory cytokine production. Study Design: the Kidd blood group antigen (Jka), was selected as a model. We investigated cytokine expression by helper T cells after stimulation by Jka peptides. Peripheral mononuclear cells were isolated from Jka primed donors producing anti-Jka antibodies and from non anti-Jka alloimmunized donors as negative controls. Four 16-mer peptides mimicking the Jka sequence, 266–293, including the Asp280 polymorphism, and overlapping each over by 12 amino acids were tested to map alloreactive T cell epitopes. A sensitive method, the real time RT-PCR, was chosen to quantify Th1- and Th2-type cytokines (respectively IL-2 and IL-4) after Jka peptide stimulations. DRB1* and DQB1* low resolution typing, and DRB1* DNA subtyping were performed. Results: lymphocytes from non anti-Jka alloimmunized donors produced low level of IL-2 or IL-4 (<10copies), while lymphocytes from all anti-Jka alloimmunized donors responded in a much higher level to at least one of the four Jka peptides. A clear Th1/Th2 dichotomy in the cytokine response was observed in this population. Indeed, among the 10 anti-Jka alloimmunized donors tested, 4 produced IL-2 alone and 6 produced IL-4 alone. Sequences among two peptides (Jka1and Jka2) were together able to elicit a response (IL-2 or IL-4) in 8 among 10 of these anti-Jka alloimmunized donors and represent a pool of immunodominant peptides. This Th1/Th2 dichotomy was not due to delays in kinetics of IL-2 and IL-4 productions. It was neither related to particular donor DRB1* or DQB1* molecules. The DRB1*01 phenotype frequency was increased (82%) in the anti-Jka alloimmunized donors as compared to the expected frequency (18%) in the caucasian population. This observation raised the question as to whether these molecules are associated to genetic susceptibility to anti-Jka alloimmunization. Conclusion: These data indicate that Th1 and Th2 subsets are associated to the specific memory humoral immune response against Jka RBCs. The cytokine pattern (IL-2 or IL-4) is characteristic of the donor, whatever the peptide tested. DRB1*01 seems to be implicated in the peptide presentation to the T lymphocyte. A detailed understanding of peptides and cytokines involved in T cell responses to Jka protein and the HLA class II molecules implicated in the peptide presentation constitutes a first step toward evaluation of peptide immunotherapy to prevent or treat anti-RBC alloimmunization.

scholarly journals Alloreactive T Cell Responses and Acute Rejection of Single Class II MHC-Disparate Heart Allografts Are under Strict Regulation by CD4+CD25+ T Cells

2005 ◽  
Vol 174 (6) ◽  
pp. 3741-3748 ◽  
Author(s):  
Soren Schenk ◽  
Danielle D. Kish ◽  
Chunshui He ◽  
Tarek El-Sawy ◽  
Eise Chiffoleau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Acute Rejection ◽  
T Cell Responses ◽  
Class Ii ◽  
Single Class ◽  
Cell Responses ◽  
Class Ii Mhc ◽  
Strict Regulation ◽  
Alloreactive T Cell
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