How to cite this article: Vet. Res. (2009) 40:06
DOI: 10.1051/vetres:2008044

Subpopulations of bovine WC1⁺ T cells rather than CD4⁺CD25 Foxp3⁺ T cells act as immune regulatory cells ex vivo

Aad Hoek¹, Victor P.M.G. Rutten^{1, 2}, Jolanda Kool¹, Ger J.A. Arkesteijn¹, Ruth J. Bouwstra³, Ildiko Van Rhijn¹ and Ad P. Koets<sup>1, 3

1</sup>  Division of Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands
²  Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, South Africa
³  Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands

Received 5 May 2008; accepted 15 October 2008; published online 18 October 2008

Abstract - Regulatory T cells (Treg) are regarded essential components for maintenance of immune homeostasis. Especially CD4⁺CD25 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⁺CD25 T cells and 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⁺CD25 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⁺CD25 T cells, WC1⁺, WC1.1⁺ and WC1.2⁺  T cells, NK cells, CD8⁺ T cells and CD14⁺ monocytes. Only the WC1.1⁺ and WC1.2⁺  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⁺CD25Foxp3⁺ and CD4⁺CD25 T cells do not function as Treg ex vivo. The bovine Treg function appears to reside in the  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.

Key words: bovine / T cells / regulation / cytokines / suppression

Corresponding author: A.Hoek@uu.nl

© INRA, EDP Sciences 2008