Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting

Nakagome, Kazuyuki; Dohi, Makoto; Okunishi, Katsuhide; To, Yasuo; Sato, Atsushi; Komagata, Yoshinori; Nagatani, Katsuya; Tanaka, Ryoichi; Yamamoto, Kazuhiko

doi:10.1186/1465-9921-6-46

Cited by 28 publications

(23 citation statements)

References 49 publications

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“…These two profiles are associated with Tem (CD44 hi CD62L lo ) or Tcm (CD44 hi CD62L hi ) (27). The presence of antigen-experienced adoptively transferred T cells in nonlymphoid organs is well documented (37,38), as is the preference for CD62L lo cells to home to nonlymphoid tissues such as the lung, because of the requirement for CD62L expression to facilitate entry into lymph nodes (32,33,39). We therefore predicted that the cells that accumulated in the lung after PIT were derived from the CD62L lo fraction.…”

Section: Resultsmentioning

confidence: 98%

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergenexperienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62L lo ) and central memory (CD62L hi ) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62L hi and CD62L lo Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4 + T cells to PIT. Most notably, allergen-reactive CD62L lo Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62L hi Th2 cells. Despite this, PIT was most potent against CD62L lo Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62L hi Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios.

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Section: Resultsmentioning

confidence: 98%

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Effector CD4 ϩ T cells are known to contribute to the development of AHR (26,36,49). Treg cells are known to inhibit both Th1 and Th2 cells in vitro (4,8,18,20,64) and in vivo (14,27,38,44,56,60).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

Burchell¹,

Wikström²,

Stumbles³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Mice were immunized as reported previously (24,28,29). Seven-week-old animals were sensitized with an i.p.…”

Section: Immunization Of Mice and Evaluation Of Allergic Airway Inflamentioning

confidence: 99%

“…Mice were challenged with an aerosolized solution of 3% OVA or PBS for 10 min from day 18 to day 20. On day 21, airway responsiveness (AR) to methacholine (Mch) was measured with the enhanced pause (Penh) system or assessed by measuring airway resistance (Raw) as described previously (24,29). Mch concentration that induced a 100% increase in Penh or Raw was expressed as PC 200 Mch (g/ml) or PC 200 Mch Raw (g/ml) as an indicator of AHR.…”

Section: Immunization Of Mice and Evaluation Of Allergic Airway Inflamentioning

confidence: 99%

IL-5-Induced Hypereosinophilia Suppresses the Antigen-Induced Immune Response via a TGF-β-Dependent Mechanism

Nakagome

Dohi

Okunishi

et al. 2007

The Journal of Immunology

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Although eosinophils play an essential role in allergic inflammation, their role has recently been under controversy. Epidemic studies suggest that hypereosinophilia induced by parasite infection could suppress subsequent Ag sensitization, although the mechanism has not been fully clarified. In this study, we investigated whether eosinophils could suppress the Ag-specific immune response in the airway. BALB/c mice were sensitized and airway challenged with OVA. Systemic hypereosinophilia was induced by delivery of an IL-5-producing plasmid. IL-5 gene delivery suppressed the Ag-specific proliferation and cytokine production of CD4+ T cells in the spleen. IL-5 gene delivery before OVA sensitization significantly suppressed airway eosinophilia and hyperresponsiveness provoked by subsequent OVA airway challenge, while delivery during the OVA challenge did not suppress them. This IL-5-induced immune suppression was abolished in eosinophil-ablated mice, suggesting an essential role of eosinophils. IL-5 treatment increased the production of TGF-β1 in the spleen, and we demonstrated that the main cellular source of TGF-β1 production was eosinophils, using eosinophil-ablated mice and depletion study. TGF-β1, but not IL-5 itself, suppressed the Ag-specific immune response of CD4+ T cells in vitro. Furthermore, IL-5 treatment enhanced phosphorylation of Smad2 in CD4+ T cells. Finally, a TGF-β type I receptor kinase inhibitor restored this IL-5-induced immune suppression both in vitro and in vivo. These results suggest that IL-5-induced hypereosinophilia could suppress sensitization to Ag via a TGF-β-dependent mechanism, thus suppressed allergic airway inflammation. Therefore, hypereosinophilia could reveal an immunosuppressive effect in the early stage of Ag-induced immune response.

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Antigen-sensitized CD4+CD62Llow memory/effector T helper 2 cells can induce airway hyperresponsiveness in an antigen free setting

Cited by 28 publications

References 49 publications

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

IL-5-Induced Hypereosinophilia Suppresses the Antigen-Induced Immune Response via a TGF-β-Dependent Mechanism

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