DEFECTIVE EXPRESSION OF P56LCK IN AN INFANT WITH SEVERE COMBINED IMMUNODEFICIENCY

Severe combined immune deficiency (SCID) is a heterogeneous disorder c haracterized by profound defects in cellular and humoral immunity. We report here an infant with clinical and laboratory features of SCID an d selective CD4 lymphopenia and lack of CD28 expression on CD8(+) T ce lls. T cells from this patient showed poor blastogenic responses to va rious mitogens and IL-2. Other T cell antigen receptor-induced respons es, including upregulation of CD69, were similarly inhibited. However, more proximal T cell antigen receptor signaling events, such as anti- CD3 induced protein tyrosine phosphorylation, phosphorylation of mitog en-associated protein kinase, and calcium mobilization were intact. Al though p59fyn and ZAP-70 protein tyrosine kinases were expressed at no rmal levels, a marked decrease in the level of p56lck was noted. Furth ermore, this decrease was associated with the presence of an alternati vely spliced lck transcript lacking the exon 7 kinase encoding domain. These data suggest that a deficiency in p56lck expression can produce a SCID phenotype in humans.