Chronic Lymphocytic Leukaemia Drives the Production of T Regulatory Cells From the CD4+ CD25- Compartment with a CD27high/CD127 Low Phenotype.

Abstract 2330

Poster Board II-307

Patients with chronic lymphocytic leukaemia (CLL) have defects in both cellular and humoral immunity including changes in the numbers and function of T regulatory cells (Tregs). The identification of Tregs is an ever-evolving field and in this study we readdressed the phenotype using the markers CD25, FoxP3 and CD127-/lo and confirmed function by classical suppressor assays in CLL patients on and off treatment. Using the combination CD4 and FoxP3 we observed increased Treg frequencies in CLL patients, in particular with advanced disease, supporting previous studies showing an increase in Tregs in CLL. However in contrast to previous studies, there was no increase in the CD25+ FoxP3+ population in CLL patients rather the increase in FoxP3 expression occurred in the CD25- compartment of CLL patients. Interestingly CLL induced a 7-fold increase in the expression of FoxP3 in CD4+CD25- T cells following short-term co-culture. The T regulatory cells in CLL patients had a significantly higher expression of CD27 compared to healthy controls and although CD127 expression was low in both healthy and CLL patients it was significantly lower in CLL patients.

Fludarabine treatment initially induced increased expression of FoxP3 in the CD4+ T cell compartment but this declined gradually to reach levels below that pre-treatment. Here we propose that CLL drives the production of Tregs from the CD4+CD25- compartment as has been shown recently in Non-Hodgkins Lymphoma (NHL) and the mechanism of induction could provide alternative avenues for treatment.