References
Query Results -- Details
MGI Accession ID: MGI:3045489
J Number: J:90903
Other Accession IDs:
Title: Inducible nitric oxide synthase in T cells regulates T cell death and immune memory.
Authors: Vig M; Srivastava S; Kandpal U; Sade H; Lewis V; Sarin A; George A; Bal V; Durdik JM; Rath S
Journal: J Clin Invest
Volume: 113
Issue: 12
Date: 2004 Jun
Year: 2004
Pages: 1734-42
Review Status: Peer Reviewed
Abstract:
The progeny of T lymphocytes responding to immunization mostly die rapidly, leaving a few long-lived survivors functioning as immune memory. Thus, control of this choice of death versus survival is critical for immune memory. There are indications that reactive radicals may be involved in this death pathway. We now show that, in mice lacking inducible nitric oxide synthase (iNOS), higher frequencies of both CD4 and CD8 memory T cells persist in response to immunization, even when iNOS(+/+) APCs are used for immunization. Postactivation T cell death by neglect is reduced in iNOS(-/-) T cells, and levels of the antiapoptotic proteins Bcl-2 and Bcl-xL are increased. Inhibitors of the iNOS-peroxynitrite pathway also enhance memory responses and block postactivation death by neglect in both mouse and human T cells. However, early primary immune responses are not enhanced, which suggests that altered survival, rather than enhanced activation, is responsible for the persistent immunity observed. Thus, in primary immune responses, iNOS in activated T cells autocrinely controls their susceptibility to death by neglect to determine the level of persisting CD4 and CD8 T cell memory, and modulation of this pathway can enhance the persistence of immune memory in response to vaccination.
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