T regulatory cells: an overview and intervention techniques to modulate allergy outcome

The current economic crisis and the fiasco at the stock market bring forth the importance of regulation. Be it Wall Street or our immune system, the indomitable presence and watchful eye of a regulator cannot be understated. The cells that perform this specialized regulator function (natural Tregs) in the immune system have gained prominence with a detailed description and characterization of their identity. We discuss in this review the role of these regulators in the context of allergic diseases and how they could be manipulated for therapeutic goals.The early report suggesting the presence of immune regulation dates back to 1905, when Paul Ehrlich and J. Morgenroth reported that immunization was not successful against self-tissues. Several decades later, R. E. Billingham et al. discovered the immunological basis of tolerance or immune regulation[1]. Using a murine skin model, they demonstrated that the mice immunized with allografts in utero were able to accept skin grafts from the allogenic mice [2]. It was in 1969, that Nishizuka and Sakakura, reported the first experiments that potentially indicated the presence of T cells with immuno-regulatory potentials [3]. However, a seminal observation in 1970 by Gershon et al. suggested the occurrence of immunological tolerance and attributed it to T cells [4]. But it took Sakaguchi et al. to characterize these regulatory cells as CD4+CD25+ natural T regulatory cells. They found that athymic BALB/c mice developed autoimmune diseases, when given a population of CD4+CD25+ T cells. Nevertheless, this phenomenon was reversed when the mice were adoptively transferred with quiescent CD4+CD25+ T cells [5] revealing their immuno-suppressive effect. Further understanding of the constitution of T regulatory cells came from the discovery of the involvement of the forkhead box P3 (foxp3) [6], also known as transcription factor Scurfin in the regulation of immune response. The original scurfy mouse model was characterized by a mutat