Terminally differentiated memory T cells are increased in patients with common variable immunodeficiency and selective IgA deficiency

Abstract

Introduction: Previous studies showed that several lymphocyte abnormalities seen in the most frequent symptomatic immunoglobulin deficiency, common variable immunodeficiency (CVID), were also observed in a genetically related asymptomatic disorder - selective IgA deficiency (IgAD). In this study we searched for abnormalities in the differentiation stages of T cells as well as for similarities of these abnormalities in CVID and IgAD patients.

Material and methods: Using flow cytometry in 80 patients with IgAD, 48 patients with CVID, and 80 control persons we determined T-lymphocyte subsets: both CD4 and CD8 were divided into the naïve CD45RO^-CD27⁺, early differentiated CD45RO⁺CD27⁺, late differentiated CD45RO⁺CD27^- and fully differentiated effector CD45RO^-CD27^- memory T cells, as well as Treg cells, defined as CD4⁺CD25highCD127low T cells.

Results: An increase of CD4⁺ and CD8⁺ late differentiated memory cells was observed comparing CVID patients to controls, as well as comparing IgAD patients to controls. In CVID patients an increase of CD4⁺ early differentiated memory cells, a decrease of CD8⁺ intermediate memory cells, and CD4⁺ and CD8⁺ naïve cells were found as well. The abnormalities in IgAD patients might be explained by higher CMV seropositivity observed in our IgAD. We confirmed the repeatedly published decrease of Treg cells in CVID patients, while Treg cells in IgAD patients were increased compared to controls.

Conclusions: Our results show T-cell activation not only in CVID, but also in IgAD patients. The increase in IgAD patients may be influenced by a more frequent CMV infection in our group of IgAD patients.

Keywords: CMV; IgA deficiency; T-lymphocyte subpopulations; common variable immunodeficiency.

Fig. 1

Gating strategy for T-cell subsets. Gating is shown for a representative healthy donor. N naïve cells (CD45RO^–CD27⁺), ED early differentiated (CD45RO⁺CD27⁺), LD late differentiated (CD45RO⁺CD27–), FD fully differentiated effector (CD45RO^–CD27^–), INT intermediate (CD45RO^–CD27^dim) memory T cells

Fig. 2

Distribution of T-lymphocyte differentiation subsets in control persons and patients with IgAD and CVID. Naïve (CD45RO^–CD27⁺) CD4⁺ and CD8⁺ cells (A, E), early differentiated memory (CD45RO⁺CD27⁺) CD4⁺ and CD8⁺ cells (B, F), intermediate memory (CD45RO^–CD27^dim) CD8⁺ cells (G), late differentiated memory (CD45RO⁺CD27^–) CD4⁺ and CD8⁺ cells (C, H), fully differentiated memory (CD45RO^–CD27^–) CD4⁺ and CD8⁺ cells (D, I). Horizontal lines indicate group medians; intergroup differences were analysed using Mann-Whitney test

Fig. 3

Frequency of Treg cells in control persons and patients with IgAD and CVID. Horizontal lines indicate group medians; intergroup differences were analysed using Mann-Whitney test