We focused on the role of T-bet and NF-κB in memory recall because of their known role in regulating IFN-γ production during primary responses. In this study, we hypothesized that rapid recall production of the effector cytokine IFN-γ by memory CD4 T cells was regulated by the enhanced activity of transcription factors.
Our results reveal a molecular mechanism for memory T cell recall through enhanced NF-κB p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity, and transplantation. Moreover, pharmacologic inhibition of NF-κB activity or peptide-mediated inhibition of NF-κB p50 translocation abrogated early memory T cell signaling and TCR-mediated effector function. We identified rapid induction of NF-κB transcriptional activity and increased engagement of NF-κB on the IFN-γ promoter at rapid times after TCR stimulation of memory compared with naive CD4 T cells. By contrast, immediate IFN-γ production by Ag-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-γ promoter. In naive CD4 T cells, IFN-γ production only occurred after sustained Ag activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation and with T-bet binding to the IFN-γ promoter as assessed by chromatin immunoprecipitation analysis. In this study, we investigated transcriptional mechanisms for rapid IFN-γ production by Ag-specific memory CD4 T cells. In such locations, access is usually facilitated by either a high-security, key-controlled system or the use of electronic access control systems such as a card reader.Memory T cells are distinguished from naive T cells by their rapid production of effector cytokines, although mechanisms for this recall response remain undefined. Unlike a master key system, where each individual lock has one individual operating key and one common master key, a maison lock is designed to be operated by every key within the system.īecause of the inherent lack of security in the maison key system, some jurisdictions prohibit the use of maison key systems in apartment and condominium complexes. Maison key systems are often found in apartment building common areas, such as main entrance or a laundry room where individual residents can use their own apartment key to access these areas.
Locksmiths may also determine cuts for a replacement master key, when given several different key examples from a given system.Ī maison key system is a keying system that permits a lock to be opened with a number of unique, individual keys. To visualize this, it can be thought of as a hierarchical chart, or a tree.Ī practical attack exists to create a working master key for an entire system given only access to a single master-keyed lock, its associated change key, a supply of appropriate key blanks, and the ability to cut new keys. Larger organizations, with more complex systems, may have several levels of master keys, where the top level key works in all of the locks in the system. For example, a standard 6 pin cylinder, which was designed to be operated by only one key, can be operated by up to 2 6 = 64 keys if there are two shear points in each chamber. The fact that some pin chambers have two shear points allows for more options when picking and it also allows for more keys to operate.
Master keyed lock systems generally reduce overall security. A far more secure (and more expensive) system has two cylinders in each lock, one for the change key and one for the master key. For example, master keyed pin tumbler locks often have two shear points at each pin position, one for the change key and one for the master key. Locks that have master keys have a second set of the mechanism used to operate them that is identical to all of the others in the set of locks. These master-keyed locks are configured to operate with two, or more, different keys: one specific to each lock (the change key), which cannot operate any of the others in the set, and the master key, which operates all the locks in the set. Usually, there is nothing different about the key, however it locks into which it will fit. Master key turning a pin tumbler lock with two shear pointsĪ master key operates a set of several locks.
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