Journal
JOURNAL OF IMMUNOLOGY
Volume 177, Issue 9, Pages 5956-5967Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.9.5956
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Funding
- NCI NIH HHS [R01 CA 86172, R01 CA086172] Funding Source: Medline
- NIAID NIH HHS [R01 AI 50150, R01 AI050150] Funding Source: Medline
- NIAMS NIH HHS [P30 AR048311, R21 AR055252, P30 AR 050948, P30 AR050948] Funding Source: Medline
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The fate of dendritic cells (DCs) after Ag presentation may be DC subset-specific and controlled by many factors. The role of activation-induced apoptosis in regulating DC function is not clear. We investigated the fate of cutaneous DCs (cDCs), specifically Langerhans cells (LCs), and observed that they undergo apoptosis after successful Ag presentation to CD4 T cells. Caspase-specific inhibitors revealed that LC lines use a type II poptosis pathway in response to CD4 T cells. In support of this, BH3-interacting domain (Bid) protein was present at high levels and specifically cleaved in the presence of Ag-specific T cells. Significant resistance to apoptosis by OT-2 CD4 cells was also observed for Bid knockout (KO) LCs in vitro. To test whether Bid was required to regulate LC function in vivo, we measured contact sensitization and topical immunization responses in Bid KO mice and observed markedly enhanced ear swelling and proliferation responses compared with wild-type mice. Furthermore, when Ag-pulsed Bid KO migratory cDCs were inoculated into wild-type recipients, an increase in both the rate and percentage of expanded OT-2 T cells expressing IFN-gamma was observed. Thus, enhanced Ag presentation function was intrinsic to Bid KO cDCs. Therefore, Bid is an important regulator of LC viability and Ag presentation function.
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