The Hygiene Hypothesis

As somebody who grew up in India, it was instructive to see how common allergic disorders are in the west. Peanut allergy, ragweed pollen allergy, dust mite allergy... resulting in conditions such as anaphylactic reactions, hay fever and asthma are all too common. These disorders are relatively uncommon in countries like India.

An interesting hypothesis has been put forward to explain this phenomenon, called the hygiene hypothesis. It goes like this.

There are four types of CD4 or Helper T cells- Th1, Th2, Th17 and Treg. The direction that an inflammatory process, say due to an infection, takes is largely determined by whether the helper cells differentiate into Th1 or Th2 cells. Treg cells are the controller cells- they tend to suppress the other subtypes.

Th1 differentiation occurs in response to IL-12 and interferon-gamma, while Th2 lineage develops mainly in response to IL-4.

In allergy, the T cell that predominates is of the Th2 subtype. Several cytokines produced by these cells contribute to particular cell types or changes vital to allergy. Thus IL-5 leads to accumulation and survival of eosinophils, IL-4 and IL-13 cause isotype switching from IgM to IgE, rather than to IgG or IgA, while IL-3 and IL-9 augment mucus secretion. IL-4 also suppresses the development of the Th1 phenotype.

It is thought that in developing countries, the numerous childhood infections that kids are subjected to, steers the development of helper T cells towards the Th1 subtype. It is thought that cytokines that promote the Th1 phenotype, such as IL-12, also suppress the development of Th2 cells, and thus protect against allergic diatheses. This is the hygiene hypothesis.

There is a major spanner in the works with this hypothesis though. Children in developing countries also carry a much higher load of various parasites, which have been clearly associated with predominance of the Th2 subtype of T helper cells. Why do then such childen not have a higher prevalence of allergic disorders, which is also subserved by Th2 cells? In fact, parasitic infestation is associated with a lower prevalence of allergies. How does one explain this?

To account for this inconsistency, another hypothesis called the counter-regulatory hypothesis has been put forward. This states that any infections, whether associated with the Th1 phenoptype, such as common bacterial chest infections in childhood, or with the Th2 phenotype, such as is found with parasitic infestations, protect against the future development of allergy. It is thought that the body responds to such infections in the long run by increasing the 4th subtype of helper T-cells, called the T regulatory or Treg cells (which carry CD4 and CD25 surface molecules and have been mentioned elsewhere on this blog). Treg cells act by damping down both Th1 and Th2 phenotypes, mainly by secreting cytokines IL-10 and TGF-beta, and it is the suppression of the Th2 phenotype that protects against allergy.