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Early programming and late‐acting checkpoints governing the development of CD 4 T‐cell memory
Author(s) -
Dhume Kunal,
McKinstry Karl Kai
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12942
Subject(s) - priming (agriculture) , antigen , biology , immune system , memory t cell , effector , epitope , immunological memory , immunology , memory cell , acquired immune system , t cell , antibody , microbiology and biotechnology , immunity , computational biology , neuroscience , botany , germination , physics , transistor , quantum mechanics , voltage
Summary CD 4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD 4 T‐cell generation into vaccine strategies therefore offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long‐term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin‐2, antigen and co‐stimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD 4 T cells to form memory during two distinct phases of the immune response. First, through ‘programming’ that occurs during initial priming, and second, through ‘checkpoints’ that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin‐2‐, antigen‐ and co‐stimulation‐dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD 4 T cells.