Foxp3 Expression in Bovine CD8⁺ T Cells Is Associated with the Intensity of CD25 Expression

Abstract

The aim of the undertaken research was to determine whether Foxp3 + CD25 + CD8 + cells exist in cattle and whether Foxp3 expression in CD8 + T cells is correlated with the intensity of CD25 expression. It has been found that 0.66 and 2.36% of CD8 + cells on average showed high and low expression of the CD25 molecule, respectively. On average, 11.61% of CD25 high CD8 + cells expressed Foxp3, while the mean percentage of Foxp3 + cells within CD25 low CD8 + cells was 3.66%. The absolute count of Foxp3 + CD25 high CD8 + cells was not significantly different from the absolute count of Foxp3 + CD25 low CD8 + cells. The obtained results indicate that CD8 + cells with the regulatory phenotype, i.e. Foxp3 + CD25 high CD8 + and Foxp3 + CD25 low CD8 + cells, occur naturally in bovine peripheral blood, although both of these subpopulations are relatively small. There is a positive correlation between the intensity of CD25 expression and the expression of the transcription Foxp3 factor in bovine CD8 + cells. Regulatory T (Treg) cells (Tregs) are heterogeneous with sub-populations which differ in their phenotype, immune inhibitory mechanisms and function. These cells are responsible for the regulation of immune response and play a leading role in developing immune tolerance through active suppression. Functions of regulatory T cells include: prevention of autoimmune diseases by maintaining self-tolerance, oral tolerance and suppression of allergy and pathogen-induced immunopathology [4, 10, 13, 14]. There are two general types of the regulatory lymphocytes: natural cells, which develop in the thymus, and induced cells, which are derived from naive lymphocytes in the periphery. Regulatory T cells consist of heterogeneous subsets which include CD4 + cells, CD8 + cells and γδ + cells. The first two types of cells can be subdivided on the basis of phenotypic or functional criteria into several subsets (e.g. Foxp3 + CD25 + CD4 + , Tr1, Th3, Foxp3 + CD25 + CD8 + , CD122 + CD8 + and CD28 − CD8 + cells [4, 10, 13, 14]). Currently, naturally-occurring CD25 + CD4 + Treg cells (nTregs) represent a major lymphocyte population maintaining dominant self-tolerance and controlling a variety of pathological immune responses. However, CD25 is not a specific marker for Tregs, because it is also expressed by activated T cells. To address this problem, scientists have been searching for marker molecules to discriminate between activated and regulatory T cells within the population of CD25-expressing CD4 + cells. In 2003, three independent groups identified the Forkhead Box P3 protein (Foxp3) as a unique marker and a "master" regulator of the development and suppressive function of CD25 + CD4 + Treg cells [5, 8, 9]. Foxp3 currently represents the most specific marker used to distinguish regulatory cells (Foxp3 + CD25 + CD4 +) from activated effector cells (Foxp3 − CD25 + CD4 +) within the CD25 + CD4 + cell subpopulation. Interestingly, Hoek et al. [7] demonstrated that bovine WC1.1 + and WC1.2 + γδ cells rather than Foxp3 + CD25 high CD4 + cells a...