Subpopulations of bovine WC1+ γδ T cells rather than CD4+CD25highFoxp3+ T cells act as immune regulatory cells ex vivo

Aad Hoek , Victor P.M.G. Rutten , Jolanda Kool , Ger J.A. Arkesteijn , Ruth J. Bouwstra , Ildiko van Rhijn , Ad P. Koets

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.

Mots clés: bovine; T cells; regulation; cytokines; suppression

Domaines: Biologie moléculaire; Génétique animale; Biologie cellulaire; Interactions cellulaires [q-bio.CB]; Microbiologie et Parasitologie; Immunologie; Neurosciences [q-bio.NC]; Santé publique et épidémiologie; Biologie animale

Aad Hoek, Victor P.M.G. Rutten, Jolanda Kool, Ger J.A. Arkesteijn, Ruth J. Bouwstra, et al.. Subpopulations of bovine WC1+ γδ T cells rather than CD4+CD25highFoxp3+ T cells act as immune regulatory cells ex vivo. Veterinary Research, 2009, 40 (1), ⟨10.1051/vetres:2008044⟩. ⟨hal-00903072⟩