Development of Autologous T Lymphocytes in Two Males with X-Linked Severe Combined Immune Deficiency: Molecular and Cellular Characterization

Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency

“…This includes normal NK-and T-cell numbers, as documented in patients with R222C, G115A, or L162R mutations, 6,8,12,13,39 normal immunoglobulins reported for patients with L271G and G115A mutations, 6,[39][40][41][42] and even normal proliferative responses except to IL-2 in 2 patients with the R222C mutation. 12,13 However, all of these patients (apart from 2 patients identified through index patients in a larger pedigree) became manifest with severe infections requiring hospitalization within the first year of life.…”

“…[6][7][8][9][10][11][12][13] In those patients, variable numbers of residual functional T cells attenuate the phenotype. The most common molecular cause for this phenomenon is hypomorphic mutations allowing sufficient function of the affected protein to generate some T cells.…”

Defective expression of the interleukin-2/interleukin-15 receptor β subunit leads to a natural killer cell–deficient form of severe combined immunodeficiency

“…18,19 Flow cytometric analysis of PBMCs showed normal expression of ␥c ( Figure 1A). Screening of the gene by (SSCP) did not reveal any abnormalities, thus making a diagnosis of X-SCID highly unlikely.…”

Inborn Errors of Human JAKs and STATs

“…The development of autologous T cells has also been reported in patients with JAK3 mutations partially permissive for JAK3 expression and for JAK3 and STAT5 phosphorylation 35 . The autologous T cells that develop in such patients display an activated phenotype and a restricted TCR repertoire indicative of very low levels of thymopoiesis and homeostatic proliferation 40,41 . However, the R222C mutation in the intracytoplasmic tail of γc is associated with normal numbers of circulating T lymphocytes, a normal polyclonal T-cell repertoire and normal thymus morphology 42,43 .…”