Immune cell dysfunction is one of the key features of the B cell malignancy Chronic Lymphocytic Leukemia (CLL) relevant to poor clinical outcomes including leukemia progression, recurrent severe infections and second malignancies. CD4+ CXCR5+ T cells in peripheral blood, known as circulating follicular helper T cells (cTfh), have specialized functional properties including ability to migrate into B cell zones and promote B cell activation. However, little is known about how cTfh impact on the pathogenesis and progression of CLL. Here we examine the phenotype, activation status, clinical relevance and potential function of cTfh cell subsets in CLL patients. Preliminary flow cytometry data demonstrate that the percentage of cTfh cells is significantly increased in CLL patients compared to healthy age matched controls. The percentage of cTfh cells is significantly higher in CLL patients with poor prognostic markers compared to patients with markers of indolent disease. Furthermore, CLL patient cTfh exhibited different composition of Tfh1, Tfh2 and Th17 subsets and showed higher expression of activation markers compared to healthy controls. Our data suggest that specific cTfh subsets are activated and expanded in CLL patients with more progressive disease. In the future, we will correlate the Tfh subset phenotype to long term clinical outcomes and investigate lymphoid tissue Tfh in CLL patients. We will also investigate the function of cTfh including cytokine and chemokine profiles as well as their migration capacity. Potentially, detailed Tfh subset profiles could serve as useful biomarker to evaluate the progression of CLL.
University of Manitoba, Dept of Immunology