TGF-beta influences the life and death decisions of T lymphocytes

TGF-beta is a powerful mediator of immune cell phenotype and function. In TGF-beta1 homozygous null mice, aberrant regulation of the immune response culminates in lethal cardiopulmonary inflammation. In dissecting the underlying mechanisms leading to the attack of self, a role for TGF-beta1 in controlling apoptosis and T cell selection patterns was uncovered. Increased levels of apoptosis and TCR mediated cell death disrupted normal negative and positive T cell selection in the thymus. Moreover, in peripheral T cell populations, increased T lymphocyte death was associated with increased expression of apoptosis-inducing receptors. Persistent activation of T cells engendered unchecked apoptosis which, rather than reducing, further exacerbated, tissue inflammation due to the absence of TGF-beta1. TGF-beta, normally generated by macrophages during clearance of apoptotic cells contributes to dampening of inflammatory sequelae associated with phagocytosis. Collectively, these data demonstrate a pivotal role for TGF-beta in multiple stages of T cell apoptosis, selection, activation and clearance.