Approaches for monitoring of non virus-specific and virus-specific T-cell response in solid organ transplantation and their clinical applications

2015 ◽  
Vol 70 ◽  
pp. 109-119 ◽  
Author(s):  
Sandra A. Calarota ◽  
Judith H. Aberle ◽  
Elisabeth Puchhammer-Stöckl ◽  
Fausto Baldanti
Keyword(s):  
T Cell ◽  
Organ Transplantation ◽  
Cell Response ◽  
Solid Organ Transplantation ◽  
Clinical Applications ◽  
T Cell Response ◽  
Solid Organ

scholarly journals Determining the Quantitative Principles of T Cell Response to Antigenic Disparity: The Case of Stem Cell Transplant Donor-Recipient Exome Wide Mismatching and HLA Bound Alloreactive Peptides

2018 ◽  
Author(s):  
Ali Salman ◽  
Vishal Koparde ◽  
Charles Hall ◽  
Max Jameson-Lee ◽  
Catherine Roberts ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Binding Affinity ◽  
Cell Response ◽  
Solid Organ Transplantation ◽  
Hla Class I ◽  
T Cell Response ◽  
Class I ◽  
Solid Organ ◽  
Cell Transplant

AbstractAlloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft versus host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 presenting an order of magnitude greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation.

Impaired Alloantigen Presenting Activity of Cord Blood Nucleated Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2203-2203
Author(s):  
Sandeep Chunduri ◽  
Dolores Mahmud ◽  
Javaneh Abbasian ◽  
Damiano Rondelli
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Solid Organ Transplantation ◽  
T Cell Response ◽  
Solid Organ ◽  
Cd34 Cells

Abstract Transplantation of HLA-mismatched cord blood (CB) nucleated cells has limited risk of severe acute graft-versus-host disease and graft rejection. This may depend on naïve T cells not yet exposed to many antigens and on immature antigen-presenting cells (APC) not delivering appropriate signals to allogeneic T cells. In order to test the APC activity of human circulating CB cells in-vitro, we initially used irradiated CB mononuclear cells (MNC) or immunomagnetically selected CD34+ cells, CD133+ cells, or CD14+ monocytes to stimulate the proliferative response of incompatible blood T cells in mixed leukocyte culture (MLC). CB MNC failed to induce allogeneic T cell proliferation, while CD34+ and CD133+ progenitors or CD14+ monocytes induced potent T cell alloresponses. Nevertheless, since allogeneic T cell response was not restored after depletion of CD3+ cells in the CB, nor the add-back of irradiated CB MNC to CD34+ or CD14+ stimulators inhibited allo-T cells, a direct suppressive effect of CB MNC was excluded. Allogeneic peripheral blood cytotoxic T-lymphocyte (CTL) responses were not induced after 7 days of stimulation with irradiated CB MNC, although after 4 weekly rechallenges with CB MNC, on average a 23% lysis of antigen-specific CB PHA-blasts was observed at the highest effector:target ratio (50:1). To test the tolerogenic potential of CB MNC, T cells initially exposed to CB MNC were rechallenged in secondary MLC with CB MNC, or CD34+ cells, or monocyte-derived dendritic cells (Mo-DC) generated in liquid culture with GM-CSF and IL-4. Allogeneic T cells were still unresponsive upon rechallenge with CB MNC, but proliferated upon 3 days of restimulation with CD34+ cells or Mo-DC from the same CB. Surprisingly, the supernatant of these latter MLCs did inhibit completely a 3rd party MLC. Instead, the supernatant of blood T cells that had been activated by CB CD34+ cells or Mo-DC both in primary and secondary MLC did not. These results show an impaired allo-APC activity of CB MNC but not CB CD34+ cells, and suggest that T cells releasing immunosuppressive cytokines may be activated by CB MNC and then expanded by a second more potent stimulation with professional APC. This hypothesis could explain the sustained engraftment of HLA-mismatched CB stem cell transplants in humans. Based on these results, the in-vivo or ex-vivo downregulation of T cell alloreactivity induced by CB MNC will be tested in experimental models of stem cell, as well as solid organ transplantation.

Impact of age and cytomegalovirus on CD8+ T-cell compartment remodeling after solid organ transplantation: A one-year follow-up study

2017 ◽  
Vol 95 ◽  
pp. 98-106 ◽  
Author(s):  
Sara Cantisán ◽  
Aurora Páez-Vega ◽  
Francisco Santos ◽  
Alberto Rodríguez-Benot ◽  
Rocío Aguado ◽  
...  
Keyword(s):  
T Cell ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Cd8 T Cell ◽  
Solid Organ ◽  
Cell Compartment ◽  
Follow Up Study ◽  
One Year

scholarly journals Factors Related to the Development of CMV-Specific CD8+ T cell Response in CMV-Seropositive Solid Organ Transplant Candidates

2015 ◽  
Vol 15 (3) ◽  
pp. 715-722 ◽  
Author(s):  
S. Cantisán ◽  
C. Rodelo-Haad ◽  
A. Páez-Vega ◽  
A. Nieto ◽  
J. M. Vaquero ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Organ Transplant ◽  
Cd8 T Cell ◽  
Solid Organ Transplant ◽  
T Cell Response ◽  
Solid Organ ◽  
Transplant Candidates

scholarly journals Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3626-3633 ◽  
Author(s):  
MN Hanson ◽  
VA Morrison ◽  
BA Peterson ◽  
KT Stieglbauer ◽  
VL Kubic ◽  
...  
Keyword(s):  
T Cell ◽  
Organ Transplantation ◽  
Virus Type ◽  
Late Complication ◽  
Solid Organ Transplantation ◽  
Lymphoproliferative Disorders ◽  
Solid Organ ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.

scholarly journals Broad and Efficient Activation of Memory CD4+ T Cells by Novel HAdV- and HCMV-Derived Peptide Pools

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander Höttler ◽  
Léo März ◽  
Maren Lübke ◽  
Hans-Georg Rammensee ◽  
Stefan Stevanović
Keyword(s):  
T Cells ◽  
T Cell ◽  
Intracellular Cytokine Staining ◽  
Solid Organ Transplantation ◽  
T Cell Response ◽  
High Morbidity ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear

Reactivation of Human Cytomegalovirus (HCMV) and Human Adenovirus (HAdV) in immunocompromised patients following stem cell transplantation (SCT) or solid organ transplantation (SOT) is associated with high morbidity and mortality. The adoptive transfer of virus-specific CD8+ and CD4+ T cells has been shown to re-establish the antiviral T-cell response and improve clinical outcome. The viral load in immunocompromised patients can efficiently be reduced solely by the infusion of virus-specific CD4+ T cells. The identification of CD4+ T-cell epitopes has mainly focused on a limited number of viral proteins that were characterized as immunodominant. Here, we used in silico prediction to determine promiscuous CD4+ T-cell epitopes from the entire proteomes of HCMV and HAdV. Immunogenicity testing with enzyme-linked immuno spot (ELISpot) assays and intracellular cytokine staining (ICS) revealed numerous novel CD4+ T-cell epitopes derived from a broad spectrum of viral antigens. We identified 17 novel HCMV-derived and seven novel HAdV-derived CD4+ T-cell epitopes that were recognized by > 50% of the assessed peripheral blood mononuclear cell (PBMC) samples. The newly identified epitopes were pooled with previously published, retested epitopes to stimulate virus-specific memory T cells in PBMCs from numerous randomly selected blood donors. Our peptide pools induced strong IFNγ secretion in 46 out of 48 (HCMV) and 31 out of 31 (HAdV) PBMC cultures. In conclusion, we applied an efficient method to screen large viral proteomes for promiscuous CD4+ T-cell epitopes to improve the detection and isolation of virus-specific T cells in a clinical setting.

scholarly journals Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2261
Author(s):  
Federica Zavaglio ◽  
Vanessa Frangipane ◽  
Monica Morosini ◽  
Elisa Gabanti ◽  
Paola Zelini ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Organ Transplant Recipient ◽  
Solid Organ ◽  
Nucleocapsid Proteins ◽  
Cell Responses ◽  
One Year

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

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