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.
Wahl
S M
SM
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4352, USA.
Orenstein
J M
JM
Chen
W
W
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D016212:Transforming Growth Factor beta