Unknown

Dataset Information

0

Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance.


ABSTRACT: Mechanisms implicated in robust transplantation tolerance at the cellular level can be broadly categorized into those that inhibit alloreactive T cells intrinsically (clonal deletion and dysfunction) or extrinsically through regulation. Here, we investigated whether additional population-level mechanisms control T cells by examining whether therapeutically induced peripheral transplantation tolerance could influence T cell populations' avidity for alloantigens. Whereas T cells with high avidity preferentially accumulated during acute rejection of allografts, the alloreactive T cells in tolerant recipients retained a low-avidity profile, comparable to naive mice despite evidence of activation. These contrasting avidity profiles upon productive versus tolerogenic stimulation were durable and persisted upon alloantigen re-encounter in the absence of any immunosuppression. Thus, peripheral transplantation tolerance involves control of alloreactive T cells at the population level, in addition to the individual cell level. Controlling expansion or eliminating high-affinity, donor-specific T cells long term may be desirable to achieve robust transplantation tolerance in the clinic.

SUBMITTER: Miller ML 

PROVIDER: S-EPMC6142813 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications


Mechanisms implicated in robust transplantation tolerance at the cellular level can be broadly categorized into those that inhibit alloreactive T cells intrinsically (clonal deletion and dysfunction) or extrinsically through regulation. Here, we investigated whether additional population-level mechanisms control T cells by examining whether therapeutically induced peripheral transplantation tolerance could influence T cell populations' avidity for alloantigens. Whereas T cells with high avidity  ...[more]

Similar Datasets

| S-EPMC8252751 | biostudies-literature
| S-EPMC5215306 | biostudies-literature
| S-EPMC3173872 | biostudies-literature
| S-EPMC4537133 | biostudies-literature
2010-09-24 | E-GEOD-18266 | biostudies-arrayexpress
| S-EPMC10694213 | biostudies-literature
| S-EPMC7408146 | biostudies-literature
| S-EPMC4498267 | biostudies-literature
| S-EPMC9561248 | biostudies-literature
2010-09-24 | GSE18266 | GEO