Regulation: the art of control? Regulatory T cells and asthma and allergy

Much is currently made of the control of asthma in therapeutic guidelines. Both the British guidelines and the Global Initiative for Asthma (GINA) define measures of control of the disease, and recent studies have defined strategies for control using available anti-inflammatory and bronchodilator therapy such as inhaled steroids and long acting β₂ agonists.^1,2 However, currently available treatments suppress inflammation but do not modify the underlying immunological predisposition to the disease.

Asthma is widely recognised as an inflammatory airway disease driven by activation of Th2-type T lymphocytes in both atopic allergic and intrinsic or non-allergic forms.^3–5 Recent advances in our understanding of the control of the immunological process have identified regulatory suppressive T cells which can prevent activation of self-reactive or pathological T cells in autoimmune or infectious disease models.^6–8 Does this understanding of immune regulation hold the prospect of disease control or even prevention for asthma?

MECHANISM OF ACTION

The interest of immunologists in actively suppressive T cells was re-awoken by the finding by Sakaguchi and co-workers that depletion of CD4+CD25+ T lymphocytes from mice led to development of autoimmune pathology which could be prevented by re-introduction of these cells.⁹ Such CD4+CD25+ regulatory T cells were active in many disease models and could reverse established inflammatory diseases such as colitis.¹⁰ These cells were shown to arise by high affinity selection in the thymus and are thought to form a “naturally occurring” regulatory population that is an important part of maintenance of tolerance or non-reactivity of the immune system against itself.^11,12 Shevach and co-workers established an in vitro system and showed that CD4+CD25+ T cells failed to proliferate to polyclonal or antigenic …