By Rideeta Raquib
Allergic reactions are common issues caused by the dysregulation of Th2 cells responses towards allergens. Normally, Th2 CD4+ T cells produce cytokines in response to allergens, and cause chronic inflammation and mucus hypersecretion, among other symptoms. Although genetics does play a role, allergic diseases, such as asthma, occur after sensitization and effector/memory T cell differentiation has taken place.
Common treatment includes avoiding any aspect that triggers the allergic disease and for respiratory diseases, β-agonists and corticosteroids are administered. These treatments may be efficient in reducing symptoms, but immune pathology is not taken into perspective. Researchers at the University of Queensland sought to halt the immune response to allergens by silencing pathogenic allergen-specific effector and memory T cells. Antigen-presenting cells (APC) are capable of overcoming tolerance defects and ceasing memory and effector CD4+ and CD8+ T cell responses. Transferring antigen-encoding BM or hematopoietic stem and progenitor cells (HSPC) utilizing mild conditioning causes a tolerogenic environment to hosts, thus can be used as therapeutic approach to prevent pathogenic TH2 responses.
Expressing antigens in APCs caused T cell tolerance and prevents antigen-specific T cell activity in Th1 conditions and this was tested under Th2 conditions in dendritic cells (DC) of mice expressing ovalbumin (OVA), a T cell dependent antigen. Non-transgenic (non-Tg) mice were also tested as a control. Spleen cells were taken from non-sensitized Tg mice and showed to produce large amounts of the cytokines IL-5 and IL-13. The mice that expressed OVA did not show any signs of sensitization based on the IL-5 and IL-13 levels. Bone marrow (BM) cells were used as a vector for allergen-encoding gene transfer. It was observed that OVA-encoding BM showed a decrease in IL-5, IL-13, and IL-4 to very low levels. Rye grass pollen (RGP) extract were also tested on non-Tg and OVA expressing mice after BM transfer showed no inhibition of IL-5 and IL-13 production, thus responses were highly antigen-specific.
Overall, it was observed that expression of allergen in DC prevents sensitization of the allergen, terminating memory Th2 cell responses. These Th2 responses that were present in sensitized subjects can be switched off by encoding BM on DC-targeted allergen expression. This study can open doors for further research in utilizing the termination of allergen-specific T cell response to tackle AAD and inflammation.
- Jane AL-Kouba, Andrew N. Wilkinson, Malcolm R. Starkey, et al. Allergen-encoding bone marrow transfer inactivates allergic T cell responses, alleviating airway inflammation. JCI Insight, 2017; 2 (11) DOI: 10.1172/jci.insight.85742
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