Local T/B cooperation in inflamed tissues is supported by T follicular helper-like cells.

Autoimmune diseases and other inflammatory conditions are characterized by large lymphocytic tissue infiltrates in which T and B cells can be found in close contact. Here, using a murine airway inflammation model, we compare antigen-specific T and B cells in lung tissue versus lung-draining lymph node. In the lung we identify a B-cell population exhibiting a classical germinal centre phenotype without being organized into ectopic lymphoid tissue. By contrast, classical CXCR5(+) Bcl-6(+) T follicular helper cells are not present. Nevertheless, lung-infiltrating T cells exhibit follicular helper-like properties including the potential to provide help to naive B cells. The lung tissue is also a survival niche for memory T and B cells remaining in residual peribronchial infiltrates after resolution of inflammation. Collectively, this study shows the importance of T/B cooperation not only in lymph nodes but also in inflamed peripheral tissues for local antibody responses to infection and autoimmunity.

ICOS-gene variants are not associated with atopic disease susceptibility in European children.

The inducible co-stimulatory molecule, ICOS, is an important regulator of T cell differentiation and effector function. Previously, it was reported that two variants in the ICOS promotor region, g.1-1413G>A and g.1-693G>A, were associated with sensitization to airborne allergens, elevated serum IgE levels and Th2 cytokine production in a Hutterite population. The aim of this study was to evaluate these two and four other selected ICOS variants for association with atopic phenotypes in two large European prospective pediatric cohorts. We investigated subjects from the German Multicenter Allergy Study (MAS), which followed over 800 children with atopic family history from birth until 13 yr of age, and from the Early Treatment of the Allergic Child Study (ETAC), which collected DNA and clinical data of over 330 children with atopic dermatitis during their first 2 yr of life. We genotyped DNA from these children by melting curve analysis using fluorescence resonance energy transfer (FRET) probes. We could not confirm the previously reported association of g.1-1413G>A and g.1-693G>A with atopic phenotypes in our pediatric cohorts. Also four other ICOS variants at putative binding sites for transcription factors showed no association with atopic dermatitis, asthma, allergic sensitization and allergic rhinitis. Our data suggest that these ICOS variants do not play a major role in the development of atopy in European children.

Inducible costimulator-positive T cells are required for allergen-induced local B-cell infiltration and antigen-specific IgE production in lung tissue.

BACKGROUND: Airway inflammation plays a critical role in the pathogenesis of asthma. In susceptible individuals, airway allergen exposure results in the recruitment of inflammatory cells into lung tissue, leading to a local inflammatory response. Central to the induction and regulation of this process are T lymphocytes. OBJECTIVE: Blocking of the newly discovered costimulatory T-cell molecule inducible costimulator (ICOS) with monoclonal antibodies was shown to ameliorate allergic airway inflammation in models of murine asthma. Although these observations indirectly support an association between ICOS and the development of allergic inflammation, the role of the ICOS + T cell in the pathogenesis of allergic airway disease remains unclear. METHODS: We used an adoptive transfer model to analyze further the role of antigen-specific ICOS + T cells during the effector phase of allergic airway inflammation. In vitro stimulated CD4 + T cells from mice transgenic for an ovalbumin-specific T-cell receptor (DO11.10) were sorted into ICOS-enriched and ICOS-depleted T-cell fractions and transferred into BALB/c recipient mice. RESULTS: Transfer of the ICOS-enriched T-cell population followed by allergen airway challenges induced pronounced infiltration of recipient T and B cells and local production of allergen-specific IgE by intrapulmonary plasma cells. In contrast, transfer of the ICOS-depleted T-cell fraction resulted in the recruitment of significantly lower numbers of B cells and no local IgE production. CONCLUSION: These data indicate that expression of ICOS defines a subset of T effector cells that are required for B-cell infiltration and local IgE production in lung tissues on allergen airway exposure.