Skewed invariant natural killer T (iNKT) cells, impaired iNKT:B-cell help and decreased SAP expression in blood lymphocytes from patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B-cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analyzed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B-cell help. Reduced total, CD4+ and remarkably, CD4-/CD8- together with those CCR5+/CXCR3+ iNKT cells were observed in the PB of CVID patients. These findings were associated with an enrichment of memory-like and a tendency towards a reduction of TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B-cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Interestingly, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B-cell help in CVID. This article is protected by copyright. All rights reserved.