T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome

Abstract

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Fig. 1

Flow cytometric analysis of peripheral blood mononuclear cells from DiGeorge syndrome (DGS; ▪) and velocardiofacial syndrome (VCFS; □) patients and from controls (▴) with 22q-unrelated congenital heart defect. Percentage (a) and absolute numbers (cells/μ l) (b) of CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺ cells. Not all the markers were studied in all tested subjects.

Fig. 2

T cell receptor (TCR) Vβ repertoire as measured by flow cytometry of thymic CD4⁺ (▪) and CD8⁺ (□) T cells from two DiGeorge syndrome (DGS) patients. Patient (a) had no significant perturbation of Vβ populations compared with normal controls (data not shown). Missing populations were shown in patient (b) (CD4 and CD8 Vβ5.2, CD4 and CD8 Vβ20). In this patient the same undetectable Vβ families were observed in peripheral T cells.