CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

Schaller, Matthew; Lundy, Steven K.; Huffnagle, Gary B.; Lukacs, Nicholas W.

doi:10.1002/eji.200425715

Cited by 46 publications

(35 citation statements)

References 44 publications

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“…Some of these effects are associated with (food) allergy and suggest that the whey hydrolysate does sensitize against whey, which is in line with the detected increased IgE levels. This includes an increased percentage of (activated) Thelper cells and a decreased percentage of cytotoxic T cells [42,43], together with an increase in activated Th2 cells [44]. The fact that despite this established sensitization no clinical symptoms were observed, suggests a stimulated immune regulatory effect of the whey hydrolysate.…”

Section: Discussionmentioning

confidence: 97%

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies

Kiewiet

Esch

Garssen

et al. 2017

Molecular Nutrition Food Res

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Scope:Partially hydrolyzed cow's milk proteins are used to prevent cow's milk allergy in children. Here we studied the immunomodulatory mechanisms of partial cow's milk hydrolysates in vivo. Methods and results: Mice were sensitized with whey or partially hydrolyzed whey using cholera toxin. Whey-specific IgE levels were measured to determine sensitization and immune cell populations from spleen, mesenteric lymph nodes and Peyer's patches after oral whey administration were measured by flowcytometry. Whey-specific IgE and IgG1 levels in partial whey hydrolysate sensitized animals were enhanced, but challenge did not induce clinical symptoms. This immunomodulatory effect of partial whey hydrolysate was associated with increased regulatory B and T cells in the spleen, together with a prevention of IgM-IgA class switching in the mesenteric lymph nodes and an increased Th1 and activated Th17 in the Peyer's patches. Conclusion: Partial hydrolysate sensitization did not induce whey-induced clinical symptoms, even though sensitization was established. Increased regulatory cell populations in the systemic immune system and a prevention of increased total Th1 and activated Th17 in the intestinal immune organs could contribute to the suppression of allergic symptoms. This knowledge is important for a better understanding of the beneficial effects of hydrolysates.

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Section: Discussionmentioning

confidence: 97%

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies

Kiewiet

Esch

Garssen

et al. 2017

Molecular Nutrition Food Res

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“…Our protocol used injections of the whole splenic T-cell population collected from DO11.10 mice, based in large part on the fact that multiple subsets of T cells, including CD4 ϩ T cells, CD8 ϩ T cells, 32 and iNKT cells, 33 are critically involved in modulating allergic asthma. The pan-T-cell "strategy" was even more relevant after we found that splenic T cells in DO11.10 donor mice were CD4 ϩ , CD8 ϩ , or double negative.…”

Section: Discussionmentioning

confidence: 99%

Adoptively Transferred Allergen-Specific T Cells Cause Maternal Transmission of Asthma Risk

Hubeau

Apostolou

Kobzik

2006

The American Journal of Pathology

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In addition to genetics and environment, maternal asthma is an identified risk factor for developing the disease during childhood. The mechanisms of this maternal effect remain poorly understood. We tested the role of allergen-specific T cells in the maternal transmission of asthma risk by modifying a model where offspring of asthmatic mothers are more prone to develop asthma after an intentionally suboptimal asthma induction. Normal BALB/c females were injected with allergen-specific T cells from ovalbumin-specific T cell receptor (TCR) transgenic DO11.10 donors before mating. Using the protocol of suboptimal asthma induction, offspring of normal and recipient mothers were tested for their susceptibility to develop asthma. Only pups of recipient mothers showed increased airway responsiveness (Penh), allergic airway inflammation with eosinophilia, and local Th2-skewed cytokine production. Although recipient mothers did not develop asthma, serum levels of interferon-␥, interleukin (IL)-4, IL-10, and IL-13 were significantly increased during pregnancy. Consistent with this finding, a subset of DO11.10 T cells persisted in the spleen and placenta of expectant recipient mothers. We conclude that allergen-specific T cells are sufficient to orchestrate the maternal transmission of asthma risk. Because overt maternal asthma was not required, our results suggest that similar maternal-fetal interactions may occur in other allergic disorders.

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“…Increased numbers of CD8+ T cells in the BAL and HLN at LIT also correlated with the resolution of airway inflammation. Suppressor CD8+ T cells have been shown to be important in the regulation of many immune responses, including airway inflammation [43,44,45]. Additionally, B cells have suppressive activity in numerous mouse models [46], including allergic airway inflammation [47, 48].…”

Section: Discussionmentioning

confidence: 99%

Accumulation of Regulatory T Cells in Local Draining Lymph Nodes of the Lung Correlates with Spontaneous Resolution of Chronic Asthma in a Murine Model

Carson¹,

Guernsey²,

Singh³

et al. 2007

Int Arch Allergy Immunol

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Background: Mice sensitized to ovalbumin develop allergic airway disease (AAD) with short-term aerosol challenge; however, airway inflammation resolves with long-term aerosol challenge, referred to as local inhalational tolerance (LIT). Methods: We sought to determine if resolution of airway inflammation correlated with increases in lymphocyte subsets in local lung compartments, including putative regulatory T cells. Results: At the AAD stage, total numbers of T and B lymphocytes in bronchoalveolar lavage (BAL) were significantly increased above controls; however, at LIT, T and B lymphocytes were significantly reduced compared to AAD. In the lung tissue, the only alteration was a significant increase in CD4+ CD25+ T cells at AAD. In the hilar lymph node (HLN), CD4+ and CD4+ CD25+ T cells were significantly increased at AAD and LIT. In addition, CD8+ T cells were significantly elevated in the HLN at LIT, and CD19+ B cells were significantly increased at AAD. Adoptive transfer of HLN lymphocytes to lymphopenic mice confirmed that AAD lymphocytes could induce airway inflammation in response to aerosol challenge, whereas LIT lymphocytes were unable to do so. Depletion of CD4+ CD25+ T cells in vivo resulted in exacerbation of inflammation at AAD and LIT. CD4+ CD25+ T cells in the HLN also displayed suppressive activity in vitro. Additionally, T cells expressing Foxp3 were increased in the BAL and HLN during LIT. Conclusions: These results indicate that lymphocytes with regulatory functions are increased and sustained in local lung compartments at LIT and that their appearance correlates with the resolution of lung inflammation.

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CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity

Cited by 46 publications

References 44 publications

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies

Adoptively Transferred Allergen-Specific T Cells Cause Maternal Transmission of Asthma Risk

Accumulation of Regulatory T Cells in Local Draining Lymph Nodes of the Lung Correlates with Spontaneous Resolution of Chronic Asthma in a Murine Model

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