ABSTRACT
A rare autosomal recessive type of severe combined immunodeficiency syndrome (SCID) that features a selective absence of CD8
T cells but abundant CD4
T lymphocytes in the peripheral blood that do not respond to T cell receptor (TCR)-mediated stimuli
in vitro
. Peripheral T cells from patients with the disorder manifest defective T cell signaling attributable to inherited mutations within the kinase domain of the TCR-associated protein tyrosine kinase (PTK) ZAP-70. ZAP-70 deficiency shows that PTKs, and especially ZAP-70, are necessary for the physiologic development and function of T cells in humans. The condition is marked by CD8 lymphocytopenia but presents during infancy with severe, recurrent, frequently fatal infections resembling those in SCID patients. The patients have normal or elevated numbers of circulating CD3
/CD4
T lymphocytes but essentially no CD8
T cells. These T cells fail to respond to mitogens or to allogeneic cells
in vitro
or to form cytotoxic T lymphocytes. By contrast, natural killer (NK) activity is normal, and they have normal or elevated numbers of B cells and low to elevated serum immunoglobulin concentrations. The thymus may have normal architecture with normal numbers of double-positive (CD4
/CD8
) thymocytes but no CD8 single-positive thymocytes. The condition results from mutations in the gene encoding ZAP-70, a non-
src
PTK important in T cell signaling.
