IL‐10 Production and CD40L Expression in Patients with Common Variable Immunodeficiency

Abstract

The authors studied CD40 ligand (CD40L) expression and interleukin‐10 (IL‐10) production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L expression, determined by using cytofluorimetry, and measured as the mean fluorescence intensity following stimulation of peripheral blood mononuclear cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12 patients, was comparable to that of controls. However, three CVI patients showed fluorescence intensity in stimulated cells below 2 standard deviations of normal donors’ mean and two other patients had only a slight increase of stimulated versus unstimulated cells (<10 channels). IL‐10 production after stimulation of PBMC with both anti‐CD3 or anti‐CD3 plus PMA gave similar results in CVI patients and normal controls. In vitro stimulation of PBMC with anti‐CD40 and various combinations of cytokines (IL‐2, IL‐4 and IL‐10) induced IgG production above 100 ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of IL‐10 production are unlikely to play a major role in the pathogenesis of impaired IgG production in most CVI patients. CD40L appears to be normally expressed in two thirds of CVI patients, but it may be functionally defective.

Impaired Secretion of IL-10 by T Cells from Patients with Common Variable Immunodeficiency–Involvement of Protein Kinase A Type I

“…There are a some previous studies of IL-10 secretion in CVID reporting enhanced IL-10 secretion from monocytes and secretion comparable to healthy controls in PBMC and purified T cell cultures (31,32). In these studies, however, supernatants were harvested after 16 -24 h. As we show in this study, these time points may not be optimal when studying the ability of T cells to secrete IL-10, as the secreted levels are considerably higher after 48 h. Furthermore, while there are reports that costimulation through the CD28 signaling pathway may correct T cell deficiencies in CVID (33), we found markedly impaired IL-10 release also in T cells costimulated with anti-CD3/anti-CD28.…”

Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency

“…Recent evidence confirms that IL-4 and IL-10 production and the frequencies of polymorphisms in these genes are comparable with healthy controls, suggesting a minor, if any, role in the pathogenesis of these diseases. 30,[44][45][46][47] Furthermore, CD40 ligand (CD40L/CD154), acting as an important component of the mechanism of Ig production, is normally expressed on stimulated T lymphocytes in a predominant proportion of CVID patients. 45,46,48 Taken together, it appears that the present abnormalities of B-cell differentiation and failure to produce normal amounts of switched immunoglobulin in CVID and IgAD are not due to defect signaling through IL-4, IL-10, or IL-21 and CD40.…”

“…30,[44][45][46][47] Furthermore, CD40 ligand (CD40L/CD154), acting as an important component of the mechanism of Ig production, is normally expressed on stimulated T lymphocytes in a predominant proportion of CVID patients. 45,46,48 Taken together, it appears that the present abnormalities of B-cell differentiation and failure to produce normal amounts of switched immunoglobulin in CVID and IgAD are not due to defect signaling through IL-4, IL-10, or IL-21 and CD40. Furthermore, the ability to undergo CSR and plasma cell differentiation when stimulated with IL-21, IL-4, and anti-CD40 mAb implies that B cells from patients with CVID or IgAD are not lacking the molecular machinery necessary for such processes.…”

Unravelling the Complexity of T Cell Abnormalities in Common Variable Immunodeficiency

“…A more complete explanation would encompass the T cell abnormalities in CVID pathogenesis. In fact, a number of T cell defects have been demonstrated in the past in a still undefined proportion of CVID patients, including decreased lymphocyte proliferation to mitogens and Ags (2), increased T cell apoptosis (11), impaired cytokine production (12,13), absent generation of Ag-primed T cells after prophylactic vaccination (14,15), and reduced expression of CD40L on activated T cells (16,17). This complex scenario of T cell deficiency probably takes a major part in influencing the clinical outcome of CVID patients.…”