γδ T Lymphocytes Coordinate Eosinophil Influx during Allergic Responses

Abstract

Tissue eosinophil infiltration, which is a hallmark of allergic and helminthic diseases, is mainly coordinated by T lymphocytes, via the production of eosinophilotactic chemokines. Among T lymphocyte subsets, lymphocytes expressing γδ T cell receptor have been determined as a key factor for eosinophil accumulation via direct and indirect mechanisms. This knowledge is strongly supported by the fact that, in different experimental models of eosinophilic airway inflammation and helminth-induced Th2 lung inflammation, an evident tissue accumulation of γδ T lymphocytes is observed. In addition, the depletion of γδ T lymphocytes is correlated with the impairment of eosinophil accumulation in inflamed tissue. γδ T lymphocytes are non-conventional T lymphocytes, which comprise a minor T lymphocyte subset, mainly distributed in the tissue, and present crucial roles in innate and acquired immune responses. γδ T lymphocytes recognize several danger- and pathogen-associated molecular pattern molecules and stress antigens in a MHC-independent fashion and can provide rapid tissue-specific responses, via the production of a wide range of chemical mediators capable to modulate other cell populations. These mediators include chemoattractant cytokines and chemokines that attract eosinophils into the tissue by either direct recognition (such as IL-5, CCL11/eotaxin), or indirect mechanisms via the modulation of αβ T lymphocytes and macrophages (through the production of interferon-γ, IL-4, and CCL2/Monocyte chemoattractant protein-1, MCP-1, for example). The present review presents an overview of how γδ T lymphocytes coordinate eosinophil accumulation in allergy, by focusing on their role in airway inflammation and by discussing the involvement of cytokines and chemokines in this phenomenon.

House Dust Mite-Specific Sublingual Immunotherapy Prevents the Development of Allergic Inflammation in a Mouse Model of Experimental Asthma

“…An evident tissue accumulation of γδ T cells was observed in different experimental models of eosinophilic airway inflammation and in the airways of allergic human subjects [31]. Experimental depletion of γδ T cells has been associated with an impairment of eosinophil accumulation in inflamed tissue [31]. Some data also imply a role of γδ T cells in neutrophil influx during airway inflammation.…”

“…Interestingly, we observed a significantly diminished proportion of γδ T cells in lung tissue after SLIT treatment while the ratio of CD4+ versus CD8+ cells and the number of regulatory T cells (CD4+CD25+Foxp3+) remained unchanged or only slightly altered compared to sham-treated animals. An evident tissue accumulation of γδ T cells was observed in different experimental models of eosinophilic airway inflammation and in the airways of allergic human subjects [31]. Experimental depletion of γδ T cells has been associated with an impairment of eosinophil accumulation in inflamed tissue [31].…”

“…Some data also imply a role of γδ T cells in neutrophil influx during airway inflammation. In nonallergic in vivo experimental models it has been shown that γδ-T cell receptor-deficient mice show decreased neutrophil accumulation due to the impairment of chemokines like CXCL1 and CXCL2 [31]. Thus, a reduction in the frequency of γδ T cells at the site of inflammation may represent part of the mechanisms by which SLIT reduces features of allergic airway inflammation.…”

Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

“…In addition to lung cancer, γδT cells are involved in several lung diseases including bacterial, viral and fungal infections, allergic disease, inflammation, and fibrosis (Cheng & Hu, ). IL‐17A produced by lung‐resident γδT cells suppresses allergic inflammation by inhibiting Th2‐driven inflammation and eosinophil influx (Murdoch & Lloyd, ; de Oliveira Henriques & Penido, ). During bacterial infection, IL‐17A derived from activated lung γδT cells recruits neutrophils, induces mature granuloma formation, or induces Th17 immune responses to perform their defense functions (Bai et al, ; Okamoto Yoshida et al, ; Ye et al, ).…”

Maternal IgG impairs the maturation of offspring intrathymic IL‐17‐producing γδT cells: Implications for murine and human allergies

“…In fact, in the absence of γδT cells (TCRγδ‐deficient mice or mice depleted of γδT cells), IgE levels are reduced compared with wild‐type (WT) or untreated mice . γδT cells promote allergic inflammation in the lungs by regulating eosinophilic infiltration and IgE production and by producing Th2 cytokines . Furthermore, γδT cells have been found in the bronchoalveolar lavage fluid (BALF) of asthmatic patients and can amplify allergic airway diseases in response to dust mites, suggesting that these cells are implicated in this pathology.…”