Abstract
Purpose of review
Despite advances in immunosuppression, allograft rejection remains a significant challenge to the long-term success of solid-organ transplantation. Whilst allorecognition pathways are clearly central to rejection, the effector mechanisms of this process are less defined. T helper (Th) type 17 cells are a recently described CD4(+) T-cell subset, and have been implicated in a range of autoimmune and inflammatory conditions that were previously thought to be Th1 mediated. In light of these developments, this review examines the relative roles of these subsets in allograft rejection.
Recent findings
Th1 cells are characterized by production of the cytokine interferon-gamma, which has recently been described as having both pro- and anti-inflammatory effects, including a role in regulatory T-cell function. A number of clinical studies show that serum and intragraft interferon-gamma levels positively correlate with episodes of acute rejection, although increased interleukin-17 expression has also been reported in transplants undergoing rejection. Interestingly, a complex interplay between Treg and Th17 development has recently been demonstrated, with transforming growth factor-beta being necessary for both.
Summary
Current data indicate the presence of both subsets during allograft rejection, although their precise role is unclear. An improved understanding of the factors that influence the differentiation and function of these cell types will assist in the development of future immunomodulatory therapies.
Despite advances in immunosuppression, allograft rejection remains a significant challenge to the long-term success of solid-organ transplantation. Whilst allorecognition pathways are clearly central to rejection, the effector mechanisms of this process are less defined. T helper (Th) type 17 cells are a recently described CD4(+) T-cell subset, and have been implicated in a range of autoimmune and inflammatory conditions that were previously thought to be Th1 mediated. In light of these developments, this review examines the relative roles of these subsets in allograft rejection.
Recent findings
Th1 cells are characterized by production of the cytokine interferon-gamma, which has recently been described as having both pro- and anti-inflammatory effects, including a role in regulatory T-cell function. A number of clinical studies show that serum and intragraft interferon-gamma levels positively correlate with episodes of acute rejection, although increased interleukin-17 expression has also been reported in transplants undergoing rejection. Interestingly, a complex interplay between Treg and Th17 development has recently been demonstrated, with transforming growth factor-beta being necessary for both.
Summary
Current data indicate the presence of both subsets during allograft rejection, although their precise role is unclear. An improved understanding of the factors that influence the differentiation and function of these cell types will assist in the development of future immunomodulatory therapies.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 23 - 29 |
| Number of pages | 7 |
| Journal | Current Opinion in Organ Transplantation |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Feb 2009 |
Keywords
- Animals
- Cell Differentiation
- Graft Rejection
- Graft Survival
- Humans
- Immunosuppressive Agents
- Interferon-gamma
- Interleukin-17
- Organ Transplantation
- Signal Transduction
- T-Lymphocyte Subsets
- Th1 Cells
- Transplantation, Homologous
- Treatment Outcome