D1.132 - Novel CD8+CD122+ Regulatory T Cells Induced by B Cells Suppress T helper 2 Response and Attenuate Eosinophilic Infiltration in Allergic Asthma

Regulatory T cells (Treg cells) play an important role in maintaining immune homeostasis. Recent studies also demonstrated the therapeutic potential of Treg cells in immune diseases. In addition to CD4⁺Foxp3⁺ Treg cells, previous studies from our team demonstrated that naïve B cells can induce the conversion of CD4⁺CD25^- T cells into CD25⁺Foxp3^- regulatory T cells, termed “Treg-of-B cells”. Further, we also identified a novel CD8⁺ Treg subset (CD8⁺ Treg-of-B cells), and their immunosuppressive function has been confirmed both in vitro and in a dextran sodium sulfate-induced colitis model. This study aims to further characterize these novel Foxp3^-CD8⁺ Treg cells and to investigate their immunomodulatory effects on T helper 2 (Th2) responses and allergic asthma in vivo.

We conducted in vitro Th2 differentiation experiments and established an ovalbumin (OVA)-induced asthma model in vivo. CD8⁺ Treg-of-B cells were cultured with Th2 cells and adoptively transferred into an asthma model to evaluate their immunomodulatory roles.

Our results showed that CD8⁺ Treg-of-B cells expressed ICOS, LAG3, OX40, GITR, PD1, CTLA4, but did not express Foxp3. Activated-CD8⁺ Treg-of-B cells secreted higher levels of IL-10, IFN-γ, and TNF-α compared to those of activated CD8⁺ T cells. In addition, CD8⁺ Treg-of-B cells exhibited a phenotype similar to CD8⁺CD122⁺ Tregs and expressed higher level of IL-10 than CD8⁺CD122⁺ Tregs. In in vitro assays, CD8⁺ Treg-of-B cells exerted suppressive effects on Th2 cell proliferation and cytokine production. In the asthma model, results showed that CD8⁺ Treg-of-B cells down-regulated airway hyperresponsiveness and decreased eosinophil infiltration in the bronchoalveolar lavage fluid (BALF). 

These findings demonstrated that CD8⁺ Treg-of-B cells exerted therapeutic potential to decrease airway hyperresponsiveness and eosinophil infiltration in a murine model of asthma.