Allergy-related changes in levels of CD8+CD25+FoxP3(bright) Treg cells and FoxP3 mRNA expression in peripheral blood: the role of IL-10 or TGF-beta

Abstract

There is an increasing body of evidence that alterations of regulatory T (Treg) cell numbers and functions lead to immune disorders. Accordingly, understanding the regulatory mechanisms that maintain peripheral regulatory T (Treg) cell homeostasis is key to the development of effective targeted biologic therapies. We previously demonstrated the effects of IL-10 or TGF-beta on distinct CD8+CD28- T cell subsets in vitro. Allergy-related changes of CD8+CD25+FoxP3(bright)Treg cells and FoxP3 mRNA expression in peripheral blood were assessed by means of multicolor flow cytometry and real-time polymerase chain reaction (RT-PCR). Co-stimulation of CD8+CD25+ T cells with anti-CD3/CD28 in the presence of either IL-10 or TGF-beta increased the frequency of CD8+CD25+FoxP3(bright)Treg cells in patients with asthma and controls. Likewise, CD8+CD25+ T cell activation with anti-CD3/CD28 and TGF-beta increased FoxP3mRNA expression in all groups. Anti-CD3/CD28 and IL-10 appeared to regulate FoxP3 mRNA expression in a phenotype-dependent manner. Specifically, co-stimulation by anti-CD3/CD28 and IL-10 markedly increased FoxP3 mRNA expression in the severe asthma group whereas it had opposite effects on this value in other groups. Taken altogether, these data suggest that IL-10 and TGF-beta may modulate FoxP3 expressions at the protein and mRNA levels in respect to their need for peripheral tolerance.