Bid and Bim Collaborate during Induction of T Cell Death in Persistent Infection

Masson, F; Kupresanin, F; Mount, A; Strasser, A; Belz, GT

Author(s): Masson, F; Kupresanin, F; Mount, A; Strasser, A; Belz, GT;
Details: Publication Year 2011-04-01,Volume 186,Issue #7,Page 4059-4066
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Upon Ag encounter, naive T cells undergo extensive Ag-driven proliferation and can differentiate into effector cells. Up to 95% of these cells die leaving a small residual population of T cells that provide protective memory. In this study, we investigated the contribution of the BH3-only family protein Bid in the shutdown of T cell responses after acute and persistent infection. Influenza virus pathogenicity has been proposed to be mediated by a peptide encoded in the basic polymerase (PB1-RF2) acting through Bid. In our experiments, we found that after acute infection with influenza virus, mice lacking Bid had normal expansion and contraction of Ag-specific CD8(+) T cells. However, in chronic gamma-herpesvirus infection, Bid-deficient virus-specific CD8(+) T cells expanded normally but failed to contract fully and were maintained at similar to 2-fold higher levels. Previously, we have demonstrated that Bim plays a prominent role in T cell shutdown in persistent infection by cooperating with the death receptor Fas, which regulates apoptosis in response to repeated TCR signaling. Bid lies at the nexus of these two signaling pathways, thus we reasoned that Bid and Bim might cooperate in regulation of T cell shutdown in persistent infection. In this study, we observed that the combined loss of Bid and Bim synergistically enhanced the persistence of CD8(+) T cells during gamma-herpesvirus infection. Thus, these data uncover a role for Bid in coordinating apoptotic signaling pathways to ensure appropriate shutdown of T cell immune responses in the setting of persistent Ag exposure. The Journal of Immunology, 2011, 186: 4059-4066.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: BH3-ONLY PROTEINS; INDUCED APOPTOSIS; IMMUNE-RESPONSE; VIRAL-INFECTION; REGULATORS BIM; DENDRITIC CELL; IN-VIVO; FAS; AUTOIMMUNITY; CONTRIBUTES
Publisher's Version: https://doi.org/10.4049/jimmunol.1001918
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-04-01 12:00:00