T lymphocytes are the cells that play an essential role in regulating immune responses. The thymus is the organ in which T lymphocytes are generated. Our laboratory has investigated molecular signals that determine cell fate during T lymphocyte development in the thymus. To this goal, we have devised a technique in which one may efficiently introduce foreign genes into immature T lymphocytes. The somatic gene-transfer into developing T lymphocytes are likely useful to restore various immunodeficiencies and to establish immune tolerance to any introduced genes. The genetically engineered immune tolerance may be applied to reduce allergies and autoimmune diseases, as well as to sustain gene therapies by allowing prolonged survival of therapeutic vectors.