In Vitro Induction of Peanut-Specific Tr1 Cells
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Laurence Pellerin, PhD, Jennifer Anne Jenks, R. Sharon Chinthrajah, MD, Arram Noshirvan, Kari C. Nadeau, MD PhD FAAAAI, Maria Grazia Roncarolo, MD, Rosa Bacchetta, MD
Rationale: IL-10 producing type 1 regulatory T cells (Tr1) express the surface markers LAG3 and CD49b, can be induced in vitro and used as cell therapy to control undesired immune responses. Peanut allergy is a life-threatening condition with no curative treatment. Our aim is to induce peanut-specific Tr1s in vitro.

Methods: Healthy controls (HC) and allergic patients undergoing peanut oral immunotherapy were included in this study. Mature (mDC) or tolerogenic (DC10) dendritic cells were differentiated as previously described (Pacciani et al., 2010) in the presence of the main peanut allergens Arah1 and Arah2. Autologous CD4+T cells were co-incubated for 14 days with DC10 (‘T10’) or with mDC (‘Tm’) in the presence of absence of IL-10, respectively. We assessed by flow cytometry the expression of the Tr1 markers LAG3 and CD49b, of the gut-homing receptor GPR15, and the anergy of the T10 compared to the Tm upon restimulation with Arah1/2.

Results: The percentages of LAG3+CD49bTr1 cells were comparable in T10 cultures from patients (10.5%) and HC (9.4%). In both T10 cultures, the percentage of Tr1 was higher than in the control Tm culture. The GPR15+ cells were enriched in the CD45RA-LAG3+CD49b+ population compared to the CD45RA- population (19.3 vs 9.2% p=0.03). T10 from HC were anergic compared to Tm.

Conclusions: We successfully induced antigen specific LAG3+CD49bTr1 cells from peanut-allergic patients and HC; those from HC were anergic. GPR15+ cells were enriched in this population, suggesting their gut-homing capacity. Further studies are ongoing to assess the functional properties of Tr1 cells established from peanut allergic patients.