COMBINED IMMUNODEFICIENCY PHENOTYPE ASSOCIATED WITH INAPPROPRIATE SPONTANEOUS AND ACTIVATION-INDUCED APOPTOSIS

Programmed death of T cells has been proposed as one of the mechanisms by which HIV induces a decline in the number and functions of T cells in advanced AIDS. In this study we report on a patient affected by a congenital form of combined immunodeficiency presenting as a profound T cell activation deficiency. Subsequently, a gradual loss of T cells occurred, eventually resulting in a classical form of severe combined immunodeficiency (SCID). In this patient a sizeable fraction of apopto tic cells was documented in the first phase of the disease by either p ropidium iodide staining or DNA fragmentation analysis. The presence o f anergic T cells of maternal origin and engrafted in the child was ex cluded by analysis of DNA polymorphic regions. At 4 years of age the p atient died of disseminated interstitial pneumopathy, while still awai ting an HLA-matched bone marrow transplantation. On the occasion of a new pregnancy in the mother, the prenatal immunological evaluation of the female fetus revealed a T-B+ SCID phenotype. This is the first obs ervation of a primary immunodeficiency associated with inappropriate a poptosis.