Impaired selective cytokine production by CD4+ T cells in Common Variable Immunodeficiency associated with the absence of memory B cells

- Selective impairment in T cell cytokine production was associated with the absence of memory B cells.
- Patients lacking memory B cells had a higher clinical severity.
- Expression of BAFFR and costimulatory molecules (ICOS and PD-1) was impaired in patients with low levels of memory B cells.

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by B cell dysfunction and decreased serum immunoglobulin. CVID patients are classified by the absence or presence of memory B cells. In addition, T cell defects have been demonstrated in only a proportion of CVID patients. The aim of this study was to evaluate the function of CD4+ T cells from CVID patients and its association with memory B cells. Patients were classified according to their Freiburg groups: group Ia and Ib, with decreased switched memory B cells (< 0.4 of PBL), and group II, with normal B cell subsets. Their T cell function was evaluated after stimulation. We observed normal and even increased CD4+ T cell proliferation in group Ia (p = 0.0277). The proliferation positively correlated with the clinical severity score (r = 0.4796). We observed lower levels of IL-17A and IL-10 in group Ia (p = 0.0177, 0.0109) and Ib (p = 0.0009, 0.0084) patients. Group Ib patients also had low levels of IL-13 and IL-9 (p = 0.0169, 0.010). Group II patients had similar cytokine production to that of the controls. BAFFR expression was reduced in groups Ia (p = 0.0001) and Ib (p = 0.0002) and showed an inverse correlation with the severity score (p = 0.0262; r = 0.5371). ICOS expression was reduced in group Ia (p = 0.0364), and PD-1 was increased in group Ib (p = 0.0432) patients. This study shows a selective impairment in cytokine production in group Ia patients, which was more extensive than in group Ib patients. The impairment was associated with BAFFR expression in B cells, with ICOS and PD-1 in T cells and, remarkably, with the absence of memory B cells and with the disease severity. Our results suggest that the evaluation of cytokine expression by T cells in combination with the study of B cell memory could be important for understand the pathogenesis of CVID patients.