The role of regulatory CD4+ CD25+ T cells in allergic diseases

Allergic/atopic diseases such as allergic rhinitis, bronchial asthma and atopic dermatitis, are mainly mediated by Th2 cells. However, the immunologic mechanisms that protect against these diseases are poorly understood. Suppressor T cells play an important role in the regulation of immune responses and the mediation of immunologic tolerance. Th3 cells produce TGF-beta, IL-10 and IL-4, and suppress activation and cytokine production of effector cells via a TGF-beta-dependent manner. T-regulatory 1 (Tr1) cells are differentiated in the presence of IL-10, produce themselves high levels of IL-10 and TGF-beta and suppress via a cell contact-independent, but IL-10-dependent mechanism. A third population of CD4(+) T cells (2-10%) express the IL-2 receptor alpha-chain (CD25) and the recently defined transcription factor Foxp3. In animal models, it has been demonstrated that these CD4(+)CD25(+) regulatory T cells (Treg) play a critical role in the prevention of tumor immunity, organ-specific autoimmunity and allograft rejection leading to transplantation tolerance. Additionally, they are involved in the control of chronic infections. CD4(+) CD25(+) Treg are also present in human peripheral blood where they inhibit the proliferation and cytokine production of activated CD4(+) CD25(-) responder T cells. In this review, we summarize the function of CD4(+)CD25(+) Treg in allergic immune responses. We show that most of the examined atopic or allergic patients also harbor CD4(+)CD25(+) Treg with intact regulatory functions as described above. In a subset of patients, CD4(+)CD25(+) Treg show less reduced proliferation and higher amounts of IL-4 and IL-10 production with no suppressing capacity apart from that of IFN-gamma.