Dysregulating the regulators

Two articles in this issue of Journal of Biology prompt a brief reflection on the regulation of adaptive immune responses. (I suspect many, if not most, non-immuno-logical readers may find immunology impenetrable, and I cannot promise that what follows will reassure them, so they may like to click over to something else – Articles by Semple on diabetes [1], or Garfield and Wray on the evolution of development [2], inter alia, may interest them. Immunologically sophisticated readers will not learn anything and may also be better advised to read something else.) Both of the articles that occasioned this excursion discuss the consequences of disrupting the regulation of the immune system. In one case the disruption is by dioxin and other aryl hydrocarbon environmental pollutants [3], in the other by helminth parasites [4]. In both cases the effect is immune suppression. Both invoke a class of cells known as regulatory T cells, although they are mentioned only peripherally in the article on helminths, the main point of which is to draw attention to recent evidence that the increasing prevalence of asthma and other allergic disorders in developed countries may reflect immune hyper-responsiveness that evolved to counter chronic immuno-suppression by parasites in less salubrious times. (Readers may recognize this as the so-called hygiene hypothesis.) Regulatory T cells are one of four known subsets of T lymphocytes all belonging to the class known as CD4 T cells after the defining (and functionally crucial) marker they all express. The three other subsets are known as T H 1, T H 2 and T H 17 cells, all of which activate other immune cells of different types and with distinct functions, defined by the distinct cytokines by which they signal to the cells they activate (this is all summarized in Figure 1 of [3], and a general account can be found in [5] and [6]). The H stands for helper (because they act on, or help, other cells). T H 1 and T H 2 cells were so named when it was first recognized that there is more than one kind of helper T cell; and T H 17 when it became clear that there is a third: the 17, with the perverse logic that so bewilders non-immunologists, stands for interleukin-17, one of the defining cytokines produced by these cells. All of these helper T cells to some extent regulate one another: T H 17 …