Role of Transforming Growth Factor 1 in Lymphocyte Development and Death

. Transforming growth factor β1 (TGFβ1) is a polypeptide growth factor known to exert multiple functions during development and in the adult stage as well (1-2). TGFβ1 knockout mice are normal at the time of birth and do not exhibit any developmental defect. After one week of birth these mice start developing multifocal inflammatory lesions and eventually die around three weeks of age (3). Further studies revealed that T lymphocytes are the primary effectors in this phenotype (Doetschman, unpublished observation). During T cell development in the thymus, T cell progenitors undergo massive proliferation and around 95% of them undergo apoptosis. Positively selected CD4CD8 double positive T cells undergo thymic selection where cells that recognize self-antigens with high affinity are induced to undergo apoptosis (negative selection) (4-5). Any perturbations in the thymic education process might lead to export of self-reactive T cells to the periphery. In order to find the role of TGFβ1 in preventing the inflammation, we have studied the lymphocyte apoptosis and proliferation.