"Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation"

Immune mechanisms are not well understood in general, let alone in mechanisms relating to asthma, a respiratory condition that can result from sensitivity to allergens, leading to increased mucus production. While there are medications and solutions to asthmatic symptoms, a more helpful application would be trying to understand the reasons, at a molecular level, for these symptoms. When asthma is triggered, CD4 T helper (Th) cells, eosinophils, mast cells, and basophils accumulate and cause an overproduction of mucus. By understanding the mechanism that causes the response, it is possible to try and prevent inflammation that leads to the easily observable response. The experiment discussed used genetically specific mice that served as an effective model for this type of research (ovalbumin- induced allergic airway inflammation model), due to the fact that it emulates what occurs in humans. Basophils from the lungs of the OVA- challenged mice were transfused into wild-type (WT) mice. It was found that primarily basophils initiate Th2 cells, as well as the fact that, after observing molecular markers CD40, CD80/86, and MHC II, basophils from the lungs were capable of absorbing antigens.

One of the things that the research attempted to address was the relationship between the OX40-OX40L interaction and Th2 initiation when basophils were studied. This interaction factors into the regulation of T cell function and activation. It was of interest because many studies dealing with immune cells in patients with mild asthma featured increased expression of OX40 and OX40L, which are ligands, or molecules that will usually bond to larger molecules.

In the results section, it was found that OX40L increased after OVA stimulation by comparison to a control group, showing it is possible that this molecule is most relevant in the early phase of asthma. Basophils (from bone marrow) were also shown to significantly express OX40L when stimulated with DNP- OVA and antiDNP IgE (an antibody). Additionally, it was discovered that blocking the OX40-OX40L interaction with Anti- OX40L reduces inflammation by comparing OVAisotype Ab mice with the mice injected with OX40L Ab. One of the things that the experiment did not completely clarify was how basophils allow T cells to differentiate into Th2 cells, it was only found that OX40L might bind OX40 and then lead to Th2 differentiation. Arguably, the most significant finding was that the percentage of CD4 IL-4 Th2 cells in BasophilOX40L group was a lot lower than the isotype Ab basophil group. This leads to the assumption that when the OX40-OX40L interaction is blocked, Th2 responses are decreased.

If I were researching this topic, I would certainly want to replicate the introduction of particular antibodies to basophils. OX40 in particular was difficult to visualize and study. I could wonder, are there any cases where even when the OX40-OX40L interaction is blocked, Th2 responses are not decreased and override the attempt to block its course?


The link to the actual article- http://www.jbc.org/content/290/20/12523.full.pdf