γδ T cells in allergic airway diseases

Abstract

Allergic diseases like atopic rhinitis, bronchial asthma and urticaria are prevalent and on the rise. T cells are known to play a fundamental role in allergic diseases through the recognition of antigen, and secretion of TH2-type cytokines like interleukins (IL) -4, -5 and -13, that not only induce the synthesis of IgE but also recruit effector cells like eosinophils and basophils into the site of allergic in¯ammation. Yet, not much has been learnt about the character of these allergen-speci®c T cells, in the target organ. Again, recent studies have suggested that in addition to the ab T-cell receptor (TCR) -bearing cells, the less common gd TCR bearing cells may play important roles in the development and perpetuation of allergic in¯ammation as effector and immunoregulatory cells. The present review focuses on the characteristics and roles of gd T cells in atopic rhinitis and asthma.In the last few decades, it has becoming increasingly evident that the prevalence of allergic diseases like allergic rhinoconjunctivitis, atopic asthma and atopic dermatitis has increased, ranging between 10 and 20% of the general population [1±3]. The chain of events that lead to the allergic immune response includes the recognition of allergen by the antigen-presenting cell (APC), antigen presentation to T cells, the production of cytokines like interleukin (IL) -4 and IL-13 by T cells, the synthesis of immunoglobulin (Ig) E by B cells, binding of the IgE to the high af®nity IgE receptor (FceRI) on the surface of mast cells, and on subsequent exposure to the allergen, the crosslinking of the bound IgE±FceRI complex with multivalent allergen resulting in the release of chemical mediators like histamine, leukotrienes and prostaglandins [4±7]. This immediate phase allergic reaction occurs within several seconds to few minutes upon encounter with antigen and the central cell in this response is the mast cell ( Fig. 1). This is followed by the late phase allergic reaction which occurs after 4±6 h with a recurrence of symptoms that persists for about 24 h. The late phase allergic reaction is largely in¯ammatory and is orchestrated by cytokines released from T lymphocytes. The T-cell-derived cytokines upregulate the expression of adhesion molecules like VCAM-1 and ICAM-1 on endothelial cells, resulting in the in®ltration of eosinophils, and basophils which subsequently release a number of soluble products like prostaglandins, leukotrienes, PAF, ECP and MBP [8,9] (Fig. 1).The reason why only a proportion of individuals develop allergic disease is not yet well understood. An increase in the level of speci®c IgE is a hallmark of atopic diseases, but the genetic basis for this is as yet unknown. Studies on the major histocompatibility complex (MHC) speci®city of allergen-speci®c T cells are limited and population studies of inheritance of atopic disorders do not suggest a dominant role for HLA genes. There is increasing evidence of a link between environmental factors like air pollution (nitrogen oxides, ozone, volatile organic compounds, etc...

IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells

“…5,6 We found that ovalbumin-specific CD8 1 T cells are responsible for suppression of the T H 2 response in regional LNs at the effector phase of allergic rhinitis. Notably, transfer of CD8 1 T cells from ovalbuminsensitized WT mice could not control infiltration of eosinophils into the nasal mucosa and the T H 2 response in regional LNs at the effector phase in IL-15KO mice, suggesting that the regulatory function in the CD8 1 T cells is totally dependent on IL-15 at the effector phase.…”

“…2 The allergic responses are largely divided into 2 phases: systemic response in the induction phase and allergic inflammation in the effector phase. [3][4][5][6] T H 2 cells and IgE specific for the allergen are generated in secondary lymphoid tissues at the induction phase after sensitization. The effector phase is characterized by sneezing, pruritus and rhinorrhea, and nasal congestion with infiltration of the nasal mucosa with inflammatory cells, including basophils, eosinophils, neutrophils, newly synthesized mast cells, and mononuclear cells, which occur at mucosa after challenge with the allergen.…”

Animal Models for Asthma: Controversial Aspects and Unsolved Problems

“…In most concepts of asthma development, the focus is on Th1 and Th2 cells and the balance between these two types of reaction. However, there is growing evidence of an important role of Á‰ cells in allergic airway diseases [12,13].…”

γδ T Cells as Regulators of Airway Hyperresponsiveness

“…In humans γδ T cells have been associated with modulating allergic inflammation [17, 21, 22]. However, little is known on how human γδ T cells influence AR in asthmatics or in patients with atopy.…”