Interleukin-10-secreting type 1 regulatory T cells in rodents and humans

Interleukin-10 (IL-10)-secreting T regulatory type 1 (Tr1)
cells are defined by their specific cytokine production profile, which
includes the secretion of high levels of IL-10 and transforming growth
factor-b (TGF-b), and by their ability to suppress antigen-specific effector
T-cell responses via a cytokine-dependent mechanism. In contrast to the
naturally occurring CD4+CD25+ T regulatory cells (Tregs) that emerge
directly from the thymus, Tr1 cells are induced by antigen stimulation via
an IL-10-dependent process in vitro and in vivo. Specialized IL-10-producing
dendritic cells, such as those in an immature state or those modulated
by tolerogenic stimuli, play a key role in this process. We propose
to use the term Tr1 cells for all IL-10-producing T-cell populations that
are induced by IL-10 and have regulatory activity. The full biological
characterization of Tr1 cells has been hampered by the difficulty in
generating these cells in vitro and by the lack of specific marker molecules.
However, it is clear that Tr1 cells play a key role in regulating adaptive
immune responses both in mice and in humans. Further work to delineate
the specific molecular signature of Tr1 cells, to determine their
relationship with CD4+CD25+ Tregs, and to elucidate their respective
role in maintaining peripheral tolerance is crucial to advance our knowledge
on this Treg subset. Furthermore, results from clinical protocols
using Tr1 cells to modulate immune responses in vivo in autoimmunity,
transplantation, and chronic inflammatory diseases will undoubtedly
prove the biological relevance of these cells in immunotolerance