| First Author | Miller ML | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 8 | Pages | 2112-2126 |
| PubMed ID | 30134172 | Mgi Jnum | J:271058 |
| Mgi Id | MGI:6278386 | Doi | 10.1016/j.celrep.2018.07.067 |
| Citation | Miller ML, et al. (2018) Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance. Cell Rep 24(8):2112-2126 |
| abstractText | 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. |
