Abstract:
Regulatory T cells (Treg) are regarded essential components for maintenance of immune homeostasis. Especially CD4+CD25high T cells are considered to be important regulators of immune
reactivity. In humans and rodents these natural Treg are characterized by their anergic nature, defined as
a non-proliferative state, suppressive function and expression of Foxp3. In this study the potential functional
role of flowcytometry-sorted bovine white blood cell populations, including CD4+CD25high T cells and γδ T cell subpopulations, as distinct ex vivo regulatory cells was assessed in co-culture suppression assays.
Our findings revealed that despite the existence of a distinct bovine CD4+CD25high T cell population, which
showed Foxp3 transcription/expression, natural regulatory activity did not reside in this cell population. In
bovine co-culture suppression assays these cells were neither anergic nor suppressive. Subsequently, the
following cell populations were tested functionally for regulatory activity: CD4+CD25low T cells, WC1+,
WC1.1+ and WC1.2+ γδ T cells, NK cells, CD8+ T cells and CD14+ monocytes. Only the WC1.1+ and
WC1.2+ γδ T cells and CD14+ monocytes proved to act as regulatory cells in cattle, which was supported
by the fact that these regulatory cells showed IL-10 transcription/expression. In conclusion, our data provide
first evidence that cattle CD4+CD25highFoxp3+ and CD4+CD25low T cells do not function as Treg ex vivo.
The bovine Treg function appears to reside in the γδ T cell population, more precisely in the WC1.1+ and
the WC1.2+ subpopulation, major populations present in blood of cattle in contrast to non-ruminant species.