T cell cytokine responses to outer membrane proteins of <i>Haemophilus influenzae</i> and the house dust mite allergens Der p 1 in allergic and non‐allergic subjects

Epton, Michael; Hales, Belinda J.; Thompson, Philip J.; Thomas, Wayne R.

doi:10.1046/j.1365-2222.2002.01523.x

Cited by 11 publications

(7 citation statements)

References 38 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, the presence of IL-4 and/or IL-13-secreting Th cells [37]. Indeed, IL-13 production by HIstimulated PBMC from both atopics and non-atopics has been reported previously for P6 [38] and IL-4 production against other undefined antigens in HI extracts has also been reported [39]. It is noteworthy in this regard that IL-4 and IL-13 are highly pleiotrophic cytokines with multiple regulatory functions beyond IgE regulation, including an important role in modulation of macrophage activity.…”

Section: Discussionmentioning

confidence: 60%

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Hollams

Hales²,

Bachert³

et al. 2010

Eur Respir J

Self Cite

View full text Add to dashboard Cite

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility.We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes.IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk.The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterialinduced inflammation.

show abstract

Section: Discussionmentioning

confidence: 60%

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Hollams

Hales²,

Bachert³

et al. 2010

Eur Respir J

Self Cite

View full text Add to dashboard Cite

show abstract

“…The sustained Th2 response to colonising bacteria could downregulate Th1 and Th17 responses which could also have a role in the production of disease 22. The second is that the IgE antibody itself can enhance antigen capture via Fcε receptors on antigen-presenting cells and increase the recruitment of antibacterial T cells which, on balance, have been shown to be polarised to Th1,23 and these could alter the education of dendritic cells and hence signals to allergen-specific T cells 24. The inverse association of the IgE to Der p 1 and Der p 2 with the antibacterial IgE points to a downregulation of the anti-allergen Th2 response.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

Hales

Chai

Elliot

et al. 2011

Thorax

View full text Add to dashboard Cite

Background Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae. Objective To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy. Methods IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood samples of children aged 1e5 years. IgE to the P6 antigen was examined for the 5-year group. The children were stratified based on HDM sensitisation and asthma at 5 years of age. Results HDM-sensitised children had lower IgG1 antibody titres to the bacterial antigens, and early responses (<3 years and before the development of HDM sensitisation and asthma) corrected for multiple antigens were significantly reduced for P4, P6 and PspC (p¼0.008, p¼0.004 and p¼0.028, respectively). Similar associations with asthma were also found (p¼0.008, p¼0.004 and p¼0.032 for P4, P6 and PspC, respectively). The IgG4 antibody titre and prevalence were similar in both HDM-sensitised and non-sensitised groups, but sensitised children had a slower downregulation of the IgG4 response. Children with asthma (27/145 at 5 years) had lower anti-P6 IgE responses (p<0.05). Conclusions HDM-sensitised children have early defective antibody responses to bacteria that are associated with asthma. Surprisingly, antibacterial IgE was associated with a reduced risk for asthma.

show abstract

“…22 To assess the presence of T cells specific for NTHi within the CCR3 þ CD4 þ T-cell population, we determined the P6-specific proliferative response in purified peripheral blood CD4 þ T cells undepleted or depleted for CCR3 þ cells. To enable sufficient separation between the rare proliferating T cells and the nonresponding population, CFSE dilution in T cells was assessed after 6 days of stimulation.…”

Section: Ccl28 Receptor Expression On Nasal Mucosa-derived T Cellsmentioning

confidence: 99%

“…Analysis revealed that the subjects mounted a response to P6 following stimulation with antigen ( Figure 4a), as published by others. 17,22 Strikingly, when CD4 þ T cells were depleted for CCR3 þ cells with FACS sorting, the proliferative response was abrogated and not different from unstimulated control cells. Similar results were also obtained by depleting CD4 þ CCR3 þ cells with magnetic beads prior to antigen stimulation (data not shown), thus showing that the reduced proliferation was not an artifact introduced by cell passage through the FACS.…”

Section: Ccl28 Receptor Expression On Nasal Mucosa-derived T Cellsmentioning

confidence: 99%

A role for CCL28–CCR3 in T-cell homing to the human upper airway mucosa

et al. 2015

View full text Add to dashboard Cite

Lymphocyte recruitment to peripheral tissues is fundamental for immune surveillance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. To address this, we analyzed the chemokines expressed in the normal human nasal mucosa and found that CCL28 is preferentially expressed at a high level on the lumenal face of vascular endothelial cells in the mucosa. Analysis of the cognate chemokine receptors revealed that close to 50% of the CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3, whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In the circulation, CCR3(+) T cells comprised a small subset that did not express homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T cells abrogated the proliferative response of human blood CD4(+) T cells against the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities relevant for the upper airways. Together, these findings indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.

show abstract

T cell cytokine responses to outer membrane proteins of Haemophilus influenzae and the house dust mite allergens Der p 1 in allergic and non‐allergic subjects

Cited by 11 publications

References 38 publications

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

A role for CCL28–CCR3 in T-cell homing to the human upper airway mucosa

Contact Info

Product

Resources

About