Dataset Information

Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

ABSTRACT: Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoire of CMV- and alloantigen-reactive T cells enriched from peripheral pre-transplant blood of 11 CMV-seropositive and HLA class I mismatched patients. Moreover, the TCR-repertoire was also analyzed in the allograft biopsies of those patients. There was a significant association between the presence of pre-transplant CMV immediate-early protein 1 (IE-1)-specific effector/memory T cells and acute renal allograft rejection and function (p = 0.01). Most importantly, we revealed shared TCR-ß sequences between CMV-IE1 and donor alloantigen-reactive T cells in all pre-transplant peripheral blood samples analyzed in CMV-seropositive patients who received HLA class I mismatched grafts. Identical TCR sequences were also found in particular in post-transplant allograft biopsies of patients with concomitant CMV infection and rejection. Our data show the presence of functional, cross-reactive T cells and their clonotypes in peripheral blood and in kidney allograft tissue. It is therefore likely that CMV-donor cross-reactivity as well as CMV specific T cell elicited inflammation is involved in the processes that affect allograft outcomes.

SUBMITTER: Stranavova L

PROVIDER: S-EPMC6834532 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

Stranavova Lucia L Pelak Ondrej O Svaton Michael M Hruba Petra P Fronkova Eva E Slavcev Antonij A Osickova Klara K Maluskova Jana J Hubacek Petr P Fronek Jiri J Reinke Petra P Volk Hans-Dieter HD Kalina Tomas T Viklicky Ondrej O

Frontiers in immunology 20191031

Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypot ...[more]

PMID: 31736968

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Dataset Information

Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

Publications

Heterologous Cytomegalovirus and Allo-Reactivity by Shared T Cell Receptor Repertoire in Kidney Transplantation.

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