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IL-2 Mediates Generalized Tfh Downregulation during Allergen-Specific Immunotherapy
Saturday, March 5, 2016: 2:45 PM
Room 408A (Convention Center)
Véronique M. Schulten, PhD, , ,
Rationale:

A key factor in mediating allergic disease is allergen-specific IgE, which is significantly impacted by IgG4 blocking antibodies induced during allergen-specific immunotherapy (AIT). T follicular helper (Tfh) cells are CD4+ T cells specialized in helping B cell differentiation and maturation. To date, no data is available on the impact of Tfh cells in allergic disease.

Methods:

The frequency of total Tfh cells (CD4+CD45RO+CXCR5+) in allergic, non-allergic and AIT-treated patients was assessed by flow cytometry. The effect of IL-2 production after a 5-day culture with anti-CD3/28 or antigenic stimulation on CXCR5 was assessed alongside CD25 expression and IL-2 levels in the supernatant.

Results:

Assessment of total Tfh cell frequency in different cohorts revealed that CXCR5 expression is broadly down-regulated during AIT compared to untreated patients. Furthermore, a generalized down-regulation was observed in response to IL-2 after TCR stimulation, which was partially reversed by anti-IL-2.

Conclusions:

Investigating Tfh populations in different donor cohorts revealed that AIT treatment reduced CXCR5 expression in Tfh cells. This down-regulation is associated with IL-2 production in an in vitro setting. Decreased CXCR5 expression could have drastic effects on the motility of Tfh cells in vivo and may impact their homing to germinal centers, where they co-localize with B cells. This may reduce B cell help and affect antibody production. Elucidating the exact mechanism by which IL-2 is involved in CXCR5 down-modulation and to what extend Tfh cell mobility and functionality is affected could give new insights into the mechanisms by which AIT modulated antibody responses.