Elevated levels of circulatory follicular T helper cells in chronic lymphocytic leukemia contribute to B cell expansion.

Chronic lymphocytic leukemia (CLL) is characterized by an expansion of mature B cells in the bone marrow, peripheral lymphoid organs, and blood. CD4 T helper (Th) lymphocytes significantly contribute to the physiopathology of CLL, but the subset(s) of Th cell involved in CLL pathogenesis is (are) still under debate. In this study, we performed flow cytometry analysis of the circulatory T cells of untreated CLL patients and observed an increase in follicular helper T cells (Tfh), which is a subset of T cells specialized in B cell help. Elevated numbers of Tfh cells correlated with disease severity as measured by the Binet staging system. Tfh from CLL patients were activated and skewed toward a Th1 profile as evidenced by their PD-1+IL-21+IFNγ+ phenotype and their CXCR3+CCR6- chemokine receptor profile. Tfh efficiently enhanced B-CLL survival and proliferation through IL-21 but independently of IFNγ. Finally, we observed an inverse correlation between the Tfh1 and IgA and IgG serum levels in patients, suggesting a role for this Tfh subset in the immune dysfunction associated with CLL. Altogether, our data highlight an impairment in circulatory Tfh subsets in CLL patients and their critical role in CLL physiopathology.

Functions of Tfh Cells in Common Variable Immunodeficiency.

Common variable immunodeficiency is the most common clinical primary immunodeficiency in adults. Its hallmarks are hypogammaglobulinemia and compromised B-cell differentiation into memory or antibody-secreting cells leading to recurrent infections. This disease is heterogeneous, with some patients harboring multiple complications such as lymphoproliferative disorders, autoimmune manifestations, or granulomatous inflammation. The mechanisms leading to these complications remain elusive despite numerous associations found in the literature. For instance, although described as a B cell intrinsic disease, numerous abnormalities have been reported in other immune cell compartments. Here, we tuned our attention to follicular helper T cells, a CD4+ T cell population specialized in B cell help, considering the recent publications showing an involvement of these cells in CVID pathogenesis.