Elevated and cross‐responsive CD1a‐reactive T cells in bee and wasp venom allergic individuals

Subramaniam, Sumithra; Aslam, Aamir; Misbah, Siraj; Salio, Mariolina; Cerundolo, Vincenzo; Moody, D. Branch; Ogg, Graham S.

doi:10.1002/eji.201545869

Cited by 51 publications

(65 citation statements)

References 42 publications

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“…For example, an increased frequency of bee and wasp venom responsive to CD1a-restricted T cells in allergic individuals was recently described [31]. Furthermore, endogenous lipids from Brazil nut can act as adjuvants for the immune response against Ber e 1 allergen and iNKT cells play a crucial role in this response [12].…”

Section: Discussionmentioning

confidence: 99%

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Gracia

López-Relaño²,

Revilla³

et al. 2017

Int Arch Allergy Immunol

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Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study wasto analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Methods: Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Results: Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Conclusions: Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses.

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Section: Discussionmentioning

confidence: 99%

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Gracia

López-Relaño²,

Revilla³

et al. 2017

Int Arch Allergy Immunol

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“…These T cells, which can secrete both IL-13 and IFN-γ in allergic patients, can be activated by the generation of novel lipid antigens by naturally occurring enzymes found in various allergen sources, as was recently described for bee venom. 155,156 Given the abundance of lipid antigens in allergens and microbes, a role for CD1a-reactive T cells in asthmatic patients is entirely plausible.…”

Section: Heterogeneity Of T Cells and Influence Of The Tissue Microenmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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“…This possibility was suggested by a provocative study showing that PLA2 in insect venom, when introduced into the dermis of the skin, can convert phospholipids into CD1a-binding fatty acids that are capable of activating autoreactive CD1a-restricted T cells [32]. Consistent with this finding, CD1a-restricted T cells were expanded in individuals allergic to bee and wasp venom [34]. Autoreactive CD1a-restricted T cells produce the cytokines IFN-γ and IL-22 [28], which contribute to antimicrobial defenses, keratinocyte proliferation and a variety of skin inflammatory diseases.…”

Section: Cd1amentioning

confidence: 82%

Mechanisms and Consequences of Antigen Presentation by CD1

Kaer

Joyce

2016

Trends in Immunology

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The CD1 proteins are a family of non-polymorphic, MHC class I-related molecules that present lipid antigens to subsets of T lymphocytes with innate- or adaptive-like immune functions. Recent studies have provided new insight into the identity of immunogenic CD1 antigens and the mechanisms that control the generation and loading of these antigens onto CD1 molecules. Furthermore, substantial progress has been made in identifying CD1-restricted T cells and decoding the diverse immunological functions of distinct CD1-restricted T cell subsets. These findings shed new light on the contributions of the CD1 antigen presentation pathway to normal health and a diverse array of pathologies, and provide a new impetus for exploiting this fascinating recognition system for the development of vaccines and immunotherapies.

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Elevated and cross‐responsive CD1a‐reactive T cells in bee and wasp venom allergic individuals

Cited by 51 publications

References 42 publications

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Pathogenic CD4 + T cells in patients with asthma

Mechanisms and Consequences of Antigen Presentation by CD1

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