During an asthmatic episode, aberrantly reactive type 2 T helper (TH2) cells aggressively recruit an assortment of leukocytes that induce airway hyperreactivity (AHR). Current models of asthma have been influenced by evidence that AHR may arise from an insufficiency of TH1 cells relative to TH2 cells. One idea is that this imbalance may have been promoted by cleaner childhood environments, because TH1 cells are known to mediate resistance to most viral and bacterial infections. Work from two groups presents an alternative scenario in which AHR may be the outcome of a breakdown of direct immune suppression by regulatory T (TR) cells.
Akbari et al. observed that T cells cocultured with pulmonary dendritic cells (DCs) presenting an artificial allergen (ovalbumin) produced the characteristic TR cytokine interleukin-10 (IL-10). After receiving DC-boosted TR cells, ovalbumin-sensitized mice did not display AHR when reexposed to ovalbumin. This alleviation of AHR could be blocked with antibodies to IL-10. Using a similar model of ovalbumin sensitization and challenge, Zuany-Amorim et al. demonstrated inhibition of AHR in mice pretreated with a killed preparation of Mycobacterium vaccae (SRP299). Here too, induction of IL-10 expression by SRP299 was required for TR cell-mediated inhibition of AHR. These studies suggest that asthma, and perhaps other allergic conditions, may be amenable to manipulation of regulatory T cell circuits. — SJS
Nature Med.8, 1024; 625 (2002).