γδ T Cells as Regulators of Airway Hyperresponsiveness

Lahn, Michael; Kanehiro, Arihiko; Takeda, Katsuyuki; Konowal, Anatole; O’Brien, Rebecca L.; Gelfand, Anna; Born, Willi K.

doi:10.1159/000053817

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…γδ T cells are innate lymphocytes that have a nonredundant role in regulating immune homeostasis. They are known to both initiate a vigorous inflammatory response upon the first sign of danger12–14 as well as control excessive inflammation by killing activated macrophages and promoting resolution from trauma 15–19. Despite the knowledge that n‐BP treatment leads to the stimulation, intended or not, of this influential subset of peripheral T lymphocytes, there has been a lack of information regarding the consequence of this chronic immune activation over time with continued n‐BP treatment in patients with osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy

Kalyan

Quabius

Wiltfang

et al. 2012

Journal of Bone and Mineral Research

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Nitrogen-bisphosphonates (n-BP), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility. However, long-term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate-associated osteonecrosis of the jaw (BAONJ). n-BP use is known to unintentionally activate a subset of innate T cells called Vg9Vd2 T cells, but the consequence of this chronic immune stimulation has remained unexplored. The primary objectives of this study were to 1) determine the fate of Vg9Vd2 T cells in osteoporotic patients on n-BP therapy as a function of time and type of therapy; 2) evaluate the proportion of Vg9Vd2 T cells in patients who had recently experienced n-BP-associated ONJ. We found there is a notable loss of Vg9Vd2 T cells over time in osteoporotic patients on n-BP therapy, particularly those on intravenous (iv) therapy (Spearman r ¼ À0.55, p < 0.0001 iv; r ¼ À0.3, p < 0.03 oral) (n ¼ 68); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on Vg9Vd2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n ¼ 6) who had experienced BAONJ were all found to be significantly deficient in Vg9Vd2 T cells (median ¼ 0.07%) in comparison to age-and sex-matched treatment-naïve controls (N ¼ 11; median ¼ 2.40%), U ¼ 0, p ¼ 0.001; this was the only consistent difference in the leukocytes assessed. All BAONJ cases had an underlying condition that further contributed to impaired immunity. We propose Vg9Vd2 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n-BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ. ß

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Section: Discussionmentioning

confidence: 99%

Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy

Kalyan

Quabius

Wiltfang

et al. 2012

Journal of Bone and Mineral Research

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“…In contrast, regulatory functions of γδT cells have been demonstrated during established disease to promote wound healing 13 , 14 . Interestingly, γδT cells are elevated in the airways of asthmatics 15 , and a regulatory γδT cells population elicited in response to allergen exposure has been observed in both mice and rats 16 , 17 . We recently demonstrated the vital contribution of IL-17 + γδT cells to resolution of acute allergic airway inflammation 18 .…”

Section: Introductionmentioning

confidence: 99%

γδT cells regulate chronic airway inflammation and development of airway remodelling

Murdoch

Gregory

Lloyd

2014

Clin Experimental Allergy

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BackgroundγδT cells play a crucial immunoregulatory role in the lung, maintaining normal airway tone and preventing hyperresponsiveness to innocuous allergen. During acute inflammatory episodes, γδT cells promote resolution of acute inflammation. However, their contribution to inflammation-associated airway remodelling remains unexplored. Here we investigate the effects of γδT cell blockade on established allergic airway inflammation and development of remodelling.MethodsSensitised mice were exposed to prolonged ovalbumin challenge or continuous house-dust mite exposure to induce chronic inflammation and remodelling. Functional blocking anti-TCRδ antibody was administered therapeutically, and parameters of airway inflammation and remodelling were examined.ResultsTherapeutic blockade of γδT cells prevented the typical resolution of acute airway inflammation characterised by elevated eosinophil and Th2 cell numbers. Moreover, the lung displayed exacerbated airway remodelling, typified by excess peribronchiolar collagen deposition.ConclusionsThese results demonstrate a unique role for γδT cells in constraining allergen-induced airway remodelling. Manipulating the γδT cell compartment may therefore contribute to strategies to prevent and treat remodelling.

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“…Protective Á‰ T cells play not only a crucial role during early immune responses to pathogens, but they are also responsible for the downregulation of immune responses during the process of an infection [7][8][9]. In addition, they are capable of regulating inflammatory reactions depending on stimulus [10] and dose [11,12]. Their protective and regulatory potential lies in their support for immunoglobin class switching (IgA) [13], induction of oral tolerance [6,14], stimulation of the innate immune system [15], regeneration of damaged epithelium [16][17][18], clearance of necrotic epithelium [2,19], and their ability to synthesize various cytokines, chemokines, and growth factors.…”

Section: Introductionmentioning

confidence: 99%

Role of Gamma Delta T Cells in Inflammatory Bowel Disease

Kühl

Loddenkemper²,

Westermann³

et al. 2002

Pathobiology

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γδ T cells have previously been shown to play a protective role in various animal models of chronic inflammation (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis, and non-obese diabetes). This immunoregulatory potential is exerted by synthesizing various anti-inflammatory cytokines and growth factors (e.g., transforming growth factor-β). As the normal balance between inflammatory and regulatory cytokines is perturbed in inflammatory bowel disease (IBD) a protective effect of γδ T cells seems likely. This notion is supported by our finding of increased mortality of rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis following γδ T cell depletion. In contrast, no effect was observed after depletion of γδ T cells in a Crohn’s disease animal model with terminal ileitis (TNF^ΔARE mice). Therefore, future studies must further define where in the intestinal immune system γδ T cells exert their protective function and how this can be used in the treatment of IBD.

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γδ T Cells as Regulators of Airway Hyperresponsiveness

Cited by 8 publications

References 30 publications

Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy

Can peripheral blood γδ T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy

γδT cells regulate chronic airway inflammation and development of airway remodelling

Role of Gamma Delta T Cells in Inflammatory Bowel Disease

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