Abstract
DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, such as autoimmune thrombocytopenia. B cells in DiGeorge syndrome show impaired maturation, with low switched-memory B cells and a wide spectrum of antibody deficiencies or dysgammaglobulinemia, presumably due to impaired germinal center responses. We set out to evaluate circulating follicular helper T cells (cTFHs) in DiGeorge syndrome, as markers of T–B interaction in the germinal centers in a cohort of 17 patients with partial DiGeorge and 21 healthy controls of similar age. cTFHs were characterized as CXCR5+CD45RA− CD4+ T cells using flow cytometry. We verify previous findings that the population of memory CD4+ T cells is relatively increased in diGeorge patients, corresponding to low naïve T cells and impaired T cell production in the thymus. The population of CXCR5+ memory CD4+ T cells (cTFHs) was significantly expanded in patients with DiGeorge syndrome, but only healthy controls and not DiGeorge syndrome patients showed gradual increase of CXCR5 expression on cTFHs with age. We did not observe correlation between cTFHs and serum IgG levels or population of switched memory B cells. There was no difference in cTFH numbers between DiGeorge patients with/without thrombocytopenia and with/without allergy. Interestingly, we show strong decline of PD1 expression on cTFHs in the first 5 years of life in DiGeorge patients and healthy controls, and gradual increase of PD1 and ICOS expression on CD4− T cells in healthy controls later in life. Thus, here, we show that patients with DiGeorge syndrome have elevated numbers of cTFHs, which, however, do not correlate with autoimmunity, allergy, or production of immunoglobulins. This relative expansion of cTFH cells may be a result of impaired T cell development in patients with thymic dysplasia.
Highlights
DiGeorge syndrome is a primary immunodeficiency characterized by thymic dysplasia and T-cell lymphopenia [1]
Our cohort of DiGeorge syndrome patients has typically low absolute T cell lymphopenia, which becomes less pronounced with age (Figure 1A)
The inability of immune system in DiGeorge syndrome to produce naïve T-cells in normal quantities has been recognized for a long time and is believed to result from thymic dysplasia
Summary
DiGeorge syndrome is a primary immunodeficiency characterized by thymic dysplasia and T-cell lymphopenia [1]. Follicular Helper T Cells in DiGeorge Syndrome failure to develop a proper niche for the generation of mature thymocytes results in T-cell lymphopenia and increased susceptibility to infection in patients with DiGeorge syndrome. The immune system has been studied thoroughly in DiGeorge syndrome, with a specific focus on T cells and their development. Taken together with information on the humoral immune compartment in DiGeorge syndrome patients, including impaired response to vaccination, hypogammaglobulinemia [12, 13], and dysfunctional maturation of B-cells [4, 14, 15], these findings reflect the dysregulation of T–B-cell interactions in DiGeorge syndrome
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