T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections

Abstract

Summary Common variable immunodeficiency disorders (CVID) are a group of heterogeneous conditions that have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X‐linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four‐colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup. There was a reduction in early differentiated CD4 and CD8 T cells and increased CD8 TEM in the CVID patients, particularly autoimmune cytopenia and polyclonal lymphoproliferation subgroups, suggesting a more activated T cell phenotype, due perhaps to an antigen‐driven process. XLA patients had significantly reduced putative follicular T cells, which may depend on B cells for survival, while no significant alterations were observed in the T cells of those with IgG subclass deficiency or selective IgA deficiency.

T-Cell Abnormalities in Common Variable Immunodeficiency

“…+ T cells and that there is a strong correlation between naive CD4 + T-cell counts and clinical features [12,13,39,40]. In this regard, when CVID patients were classified on the basis of clinical phenotypes (infection only, polyclonal lymphoid proliferation, cytopenias, organ-specific autoimmunity, lymphoid malignancy, and enteropathy), the autoimmune cytopenia and organ-specific autoimmunity groups had the most significantly reduced naive CD4…”

“…However, an alteration in the frequency and function of T cells has also been demonstrated in patients with CVID [12][13][14]. The influence of these defects on the interaction between T and B cells could explain not only defective antibody production, but also the development of other complications, including recurrent bacterial and viral infections, gastrointestinal disease, lymphoma, autoimmunity, inflammation, and early-onset bronchiectasis in CVID patients [15][16][17].…”

“…Traditionally, the T-cell abnormalities that characterize CVID included a reduced T-cell count, decreased lymphocyte proliferation in response to mitogens and antigens, defective T-cell signaling, decline of regulatory T cell (Tregs) counts, uncontrolled T-cell polarization, elevated levels of T-cell activation markers, and abnormality in cytokine production secondary to gene polymorphisms [12][13][14][21][22][23][24][25][26].…”

“…+ and RTE T-cell counts was most pronounced in CVID patients with autoimmune cytopenia or polyclonal lymphoid proliferation [13,39]. Several studies showed that the severity and prognosis of CVID is reflected in a parallel loss of naive CD4…”

“…+ T-cell counts, followed by the polyclonal lymphoid proliferation group [13]. Therefore, a new classification system based on naive CD4 + T-cell counts was proposed, and CVID patients were divided into 3 separate groups.…”