Flow cytometric analysis of TCR Vbeta repertoire in patients with 22q11.2 deletion syndrome.

摘要

In 22q11.2 deletion patients, the normal decrease in T lymphocyte counts after 1-2 years is blunted such that relatively T lymphocyte numbers increase over early childhood, probably via post-thymic expansion of peripheral lymphocytes. This may leave less T lymphocyte receptor (TCR) diversity than when derived from naive thymic emigrants. We analysed TCR Vbeta repertoire on 27 22q11.2 chromosome deletion patients. No patient had infection at sampling. CD3(+) CD4(+) recent thymic emigrants (RTEs) were identified by CD45RA and CD31 expression. TCR Vbeta repertoire was determined using four-colour flow cytometry. Patients and controls showed significant TCR Vbeta family usage differences between CD3(+) CD4(+) and CD3(+) CD4(-) T lymphocyte subpopulations. Vbeta family abnormalities (+/-3 SD of controls) were identified in 18/27 (67%) patients and 12/47 (25%) controls. In patients, the magnitude of expansions was increased, with some Vbeta families representing 37% of the cells present in the subpopulations. There was a significant increase in frequency of abnormalities in CD3(+) CD4(+) (P < 0.001) and CD3(+) CD4(-) T lymphocytes (P < 0.05) in patients. A total of 11/16 patients had an abnormal CD4(+) CD25(Bright) TCR Vbeta repertoire. There was no difference in expansions/contractions between CD4(+) CD25(Bright) and CD4(+) T lymphocyte repertoires (P = 0.575) for individual patients but significant differences in expansions/contractions between CD4(+) CD25(Bright) and CD8(+) T lymphocytes repertoires (P = 0.011). There was bias in Vbeta usage between CD3(+) CD4(+) and CD3(+) CD4(-) T lymphocyte subsets. A total of 67% patients had TCR Vbeta repertoire abnormalities, with a trend towards increased repertoire abnormalities with fewer RTEs, suggesting thymic output plays an important role in TCR repertoire diversity. There was no correlation between skewed repertoire and symptoms of infection or autoimmunity.